Chienomoto Investigator-Initiated Trials
Collaboration Directions

Population

Ages 12–36 months, delay in language or global development (suggested by delay on the Gesell language domain or S-S method), with hearing loss and clear genetic/metabolic disease excluded. Currently receiving or about to start early intervention training. n=30–50

Primary endpoint

24-week change in the Gesell Developmental Schedule language domain developmental index

Secondary endpoints

Adaptive, personal-social, and fine/gross motor domains; CDI infant language questionnaire vocabulary count; sleep; feeding; parenting stress (PSI-SF)

Safety endpoints (important)

Growth curve (height, weight, head circumference), feeding and elimination status, adverse events

Design

Parallel control with "early intervention training only," 24 weeks

Publication angle

Ages 1–3 are a critical period for language and neurodevelopment, but very few supportive options exist for this age group. Either a developmental clinic or rehabilitation department can lead; since children are already attending regular visits and training, follow-up adherence is very high

This is currently the only applicable age range for the No. 1 product. Safety and growth monitoring in this young age group must be rigorous, and we recommend the protocol be jointly reviewed by our medical department and specialists.

Population

Ages 12–36 months, preterm birth (<34 weeks), low birth weight, history of hypoxic-ischemic encephalopathy or neonatal brain injury, with Gesell or Bayley suggesting developmental delay or borderline delay. n=40–60

Primary endpoint

Bayley-III or Gesell cognitive, language, and motor domain developmental indices

Secondary endpoints

BISQ infant sleep questionnaire, CBCL 1.5–5 emotional/behavioral, feeding status, parenting stress

Safety endpoints (important)

Growth curve, adverse events

Design

Prospective cohort + parallel control, 24 weeks. Continued cohort follow-up to age 3 is recommended

Publication angle

High-risk infant follow-up clinics already have an established visit rhythm and assessment structure, so the marginal cost of data collection is extremely low. If the cohort can be followed to age 3 for outcome assessment, the value doubles

Population

Ages 6–16, on standard treatment with methylphenidate or atomoxetine for 4+ weeks at a stable dose, SNAP-IV still moderate or higher; or cases requiring dose reduction due to decreased appetite, insomnia, or mood rebound. n=40–60

Primary endpoint

Change in SNAP-IV parent-rated total score at 12 weeks

Secondary endpoints

BRIEF executive function, CSHQ sleep, appetite and weight change, change in primary medication dose, CGI-I

Design

Open-label self-controlled pre/post, or non-randomized parallel control with "original treatment only," 12 weeks

Publication angle

Partial response and the dose-reduction dilemma are among the most common yet least-studied real-world scenarios in domestic ADHD clinics

Population

Ages 6–14 with ADHD, CSHQ total score ≥41 (suggesting sleep problems), stable treatment plan. n=40–60

Primary endpoint

CSHQ total score and sleep-onset latency subscale

Secondary endpoints

Sleep diary (bedtime, number of night wakings), next-day SNAP-IV attention subscale, parent-rated sleep quality

Design

Open-label pre/post control or randomized control, 8–12 weeks

Publication angle

Sleep problems in ADHD are bidirectionally linked with stimulant use and are the single biggest factor undermining parental medication adherence. Domestic data are scarce

Population

ADHD children who habitually stop or reduce medication during long school breaks. n=40–60

Primary endpoint

SNAP-IV and frequency of emotional outbursts during the medication holiday

Secondary endpoints

Weight catch-up, sleep, parent-child conflict frequency, smoothness of medication resumption after school restarts

Design

Randomized to "medication holiday + Chienomoto" vs. "medication holiday only," 8 weeks (covering the whole break)

Publication angle

Feasibility is extremely high — the recruitment window is concentrated, the follow-up period completes naturally, and parental motivation is very strong. In addition, "management of medication holidays" has been almost entirely unstudied in Japan

Population

Ages 8–16, with ADHD inattentive-type or borderline attention problems, prominent daydreaming, slow movement, sluggish responses, and daytime sleepiness (positive on the Barkley SCT scale), regardless of concurrent stimulant treatment. n=40–60

Primary endpoint

Barkley Cognitive Disengagement Syndrome Scale (SCT/CDS parent form) total score

Secondary endpoints

ESS child sleepiness, SNAP-IV attention subscale, BRIEF executive function, teacher rating of classroom behavior, CPT reaction time and variability

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

CDS is the most closely watched new concept in child psychiatry internationally over the past 5 years (renamed from SCT); it is partly independent of ADHD and responds poorly to stimulants — precisely the "medication doesn't work" population. Domestic clinical research is nearly nonexistent, making this one of the most novel directions on this list

Population

Ages 3–12 with ASD, ABC Irritability subscale ≥18 or emotional outbursts ≥3 times/week, not on antipsychotics or on a stable dose. n=30–50

Primary endpoint

ABC Irritability subscale (ABC-I)

Secondary endpoints

ARI Affective Reactivity Index, outburst frequency diary, parenting stress scale (PSI-SF), CGI-I

Design

Open-label pre/post control, 12 weeks

Publication angle

First-line medications for irritability in ASD (risperidone/aripiprazole) carry prominent metabolic side effects and strong parental resistance. The clinical need for a non-pharmacological adjunct is clear

Population

Ages 3–12 with ASD, CSHQ ≥41 or sleep-onset latency >30 minutes. n=30–50

Primary endpoint

CSHQ total score

Secondary endpoints

Sleep diary, actigraphy (if available at the site), daytime behavioral problems, parental sleep and mood

Design

Open-label pre/post control, or randomized control against standard sleep-hygiene education, 8–12 weeks

Publication angle

Options beyond melatonin are extremely limited. Being able to make parental sleep improvement a shared endpoint is a bonus

Population

Ages 4–16, confirmed epilepsy diagnosis, anti-seizure medication (ASM) regimen stable for 3+ months, seizure control stable over the past 3 months, with a chief complaint of mood, sleep, or cognitive issues. n=40–60

Primary endpoint

Cognition (digit span + trail-making, or a brief Wechsler form) and BRIEF executive function

Secondary endpoints

SCARED/DSRS-C mood, CSHQ sleep, QOLCE quality of life, caregiver burden

Safety endpoints (important)

Seizure frequency change, ASM blood levels (if routinely monitored at the site), ASM dose adjustments — must be clearly defined and recorded throughout

Design

Open-label pre/post control, 12–24 weeks. An "ASM only" control arm strengthens the case

Publication angle

Epilepsy comorbidity is a recognized clinical gap in Japan, and "safety of a supplementary food product in children with epilepsy" can itself become an independent publication

Notes

The safety design for this direction must be rigorous, and we recommend the protocol be jointly reviewed by our medical department and specialists

Population

Ages 6–16 with chronic tic disorder or Tourette syndrome, stable treatment plan. n=30–50

Primary endpoint

YGTSS total score

Secondary endpoints

Comorbid ADHD symptoms (SNAP-IV), obsessive-compulsive symptoms (CY-BOCS), sleep, CGI-I

Design

Open-label pre/post control, 12 weeks

Publication angle

Because tic disorders fluctuate substantially, we recommend extending the baseline observation period by 2–4 weeks to control for natural variability. This design refinement can itself be a methodological highlight

Population

Ages 2.5–6 with GDD/language delay, receiving systematic rehabilitation training 3+ times weekly. n=30–50

Primary endpoint

Gesell Developmental Schedule or GDS language/adaptive domain

Secondary endpoints

S-S language development assessment, engagement rating during training (therapist-rated), sleep, caregiver burden

Design

Parallel control with "rehabilitation training only," 12–24 weeks

Publication angle

Easiest to implement in rehabilitation medicine — children are already attending training multiple times a week, so follow-up cost is near zero and attrition is extremely low

Notes

The lower age bound must match the product's applicable age range; confirm with us before enrollment

Population

Ages 2.5–8 with GDD/ASD/cerebral palsy, receiving intensive rehabilitation training 3+ times weekly, with therapists reporting "engagement drops quickly in the second half of the session." n=30–50

Primary endpoint

Effective participation time per training session (stopwatch-timed by the therapist, objective and cost-free) + PedsQL Multidimensional Fatigue Scale (parent form)

Secondary endpoints

Training engagement rating, training completion rate, parent-observed post-training fatigue, sleep, Gesell/GDS developmental domains

Design

Parallel control with "rehabilitation training only," 12 weeks

Publication angle

"Training tolerance" is the ceiling on rehabilitation volume — training volume determines outcome, and fatigue determines training volume. No one has systematically studied this causal chain, yet every rehabilitation therapist feels it, and it resonates strongly with specialists

Positioning of this domain: Antidepressants can resolve core mood symptoms, but residual symptoms (cognition, sleep, fatigue, somatization) are the main drivers of relapse and incomplete functional recovery, for which pharmacological options are limited. This is Chienomoto's primary battleground.

Population

Ages 8–14, normal intelligence, with reading/writing/math difficulty or executive function complaints, not meeting criteria for an ADHD diagnosis. n=40–60

Primary endpoint

BRIEF executive function total score + continuous performance test (CPT, if available)

Secondary endpoints

Academic self-rating, teacher rating, mood and sleep

Design

Randomized control (waitlist control), 12 weeks

Publication angle

This borderline population is easy to recruit from, and suits interdisciplinary education-medicine journals

Population

Primary caregivers (mostly mothers) of children with ADHD/ASD/GDD, PSI-SF or ZBI suggesting moderate-to-severe burden. n=40–60

Primary endpoint

Caregiver burden scale (PSI-SF / ZBI)

Secondary endpoints

Caregiver PHQ-9, GAD-7, PSQI, family functioning (FAD)

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

Shifting the lens to caregivers means very little competition. Acceptance rates are high in nursing and psychology journals, and enrollment is extremely fast (caregivers themselves are highly motivated, and follow-up adherence is far higher than for the child patients)

Population

Ages 6–16, confirmed epilepsy diagnosis, anti-seizure medication (ASM) regimen stable for 3+ months with seizure control stable over the past 3 months; complaints of decreased attention, slowed responses, memory decline, or academic slippage (more common with topiramate, valproate, or levetiracetam). n=40–60

Primary endpoint

12-week BRIEF parent-form executive function total score + digit span (working memory)

Secondary endpoints

Trail Making Test A/B or CPT reaction time and variability, teacher rating of classroom performance, PedsQL Multidimensional Fatigue Scale, QOLCE-55 quality of life, change in academic performance

Safety endpoints (important)

Change in seizure frequency and type, ASM dose adjustments, ASM blood levels (if routinely monitored at the site), adverse events

Design

Open-label self-controlled pre/post, 12–24 weeks; where feasible, add a parallel "ASM regimen only" control arm

Publication angle

"The seizures are controlled, but the child has gotten slower" is the most common — and most unresolved — complaint in pediatric epilepsy clinics. Dose reduction carries relapse risk, parents are reluctant, and clinically there is little to do but wait. Intervention studies treating cognitive comorbidity as an independent primary endpoint are nearly nonexistent domestically

Division of labor across the epilepsy line's four directions: K1 cognition and attention (No. 3), K2 medication-related irritability (No. 2), K3 anxiety/depression (No. 2), K4 sleep (No. 2). All four share the same clinic population and the same baseline assessment set, so they can run in parallel or be filed together as an "epilepsy comorbidity series."

Population

Ages 4–16 with epilepsy who developed irritability, aggressive behavior, mood instability, or markedly increased crying after starting levetiracetam (or another ASM), clearly reported by parent or teacher; ASM regimen stable for 4+ weeks with no planned medication change in the near term. n=40–60

Primary endpoint

12-week ABC Irritability subscale (ABC-I) or CBCL Externalizing behavior subscale

Secondary endpoints

Emotional-outburst frequency diary, SCARED/DSRS-C, CSHQ sleep, parent-child conflict frequency, PSI-SF (parenting stress), CGI-I, and rate of medication switching or dose reduction due to mood/behavioral side effects

Safety endpoints (important)

Seizure frequency, ASM dose adjustments and blood levels, serious behavioral events, adverse events

Design

Open-label pre/post control, or parallel control with "original regimen plus routine counseling only," 12 weeks

Publication angle

Levetiracetam's behavioral side effects are not uncommon in children and are among the leading reasons for discontinuation or switching, yet clinically there is little option beyond switching medication (evidence for pyridoxine is weak). "Switching risks relapse, but not switching means the child can't function at school" is the most classic dilemma here. The "medication-switch rate" endpoint is especially persuasive — it is a pure clinical-decision endpoint, harder than any rating scale

Must not suggest that switching medication can be prevented or replaced. If a serious behavioral adverse event occurs, clinical safety takes priority, with withdrawal per protocol-defined rules.

Population

Ages 8–16, confirmed epilepsy diagnosis, regimen stable for 3+ months, SCARED or DSRS-C at or above the cutoff; not on antidepressants, or on a stable dose for 8+ weeks. n=40–60

Primary endpoint

12-week SCARED anxiety total score (or DSRS-C depression total score, pre-selected based on the presenting complaint)

Secondary endpoints

Seizure-related fear and stigma assessment, QOLCE-55 quality of life, school attendance and social avoidance, CSHQ sleep, parental anxiety level

Safety endpoints (important)

Seizure frequency, ASM dose and blood levels, change in antidepressant use, adverse events

Design

Open-label pre/post control, or randomized control (against standard health education), 12 weeks

Publication angle

Anxiety and depression comorbidity rates in children with epilepsy are far higher than in the general pediatric population, yet pediatric neurologists are generally cautious about prescribing SSRIs to these children (concerns about seizure threshold and drug interactions), and psychiatric referral rates remain low — this population effectively falls into a vacuum between two departments, a textbook case of "need exists, population exists, no solution exists"

Mood-risk screening must be completed before enrollment. Patients with moderate-to-severe depression or self-harm risk are excluded from this study and referred directly to psychiatry, with the referral pathway documented in the protocol.

Population

Ages 4–16 with epilepsy, ASM regimen stable for 3+ months, CSHQ ≥41 or sleep-onset latency >30 minutes; sleep-disordered breathing requiring specialist management already excluded. n=40–60

Primary endpoint

12-week CSHQ total score

Secondary endpoints

Sleep diary (sleep-onset latency, number and duration of night wakings), daytime sleepiness, BRIEF and attention, mood, primary caregiver PSQI

Safety endpoints (important)

Seizure frequency (especially nocturnal seizures), ASM dose and blood levels, adverse events

Design

Open-label pre/post control, or randomized control (against sleep-hygiene education), 12 weeks

Publication angle

Sleep and seizures form a bidirectional loop — poor sleep triggers seizures, and seizures (plus ASMs) in turn disrupt sleep architecture. Clinicians all know this loop, yet almost no non-pharmacological intervention studies exist. Options beyond melatonin are essentially absent, and melatonin use itself remains debated in children with epilepsy

Nocturnal seizures are easily confused with ordinary night wakings, so the protocol must specify criteria for parents to distinguish them, ideally supported by video or event recording.

Population

Ages 5–12 with SeLECTS, seizures controlled or infrequent, but with reading, writing, language, or attention problems (teacher or parent reports academic slippage). n=30–50

Primary endpoint

24-week BRIEF executive function total score + language/reading assessment (or standardized academic score)

Secondary endpoints

Brief Wechsler working memory and processing speed index, CSHQ sleep, SCARED/DSRS-C mood, teacher rating of classroom performance

Safety endpoints (important)

Seizure frequency, follow-up EEG discharge index (if routinely rechecked at the site), ASM dose adjustments, adverse events

Design

Open-label pre/post control, or parallel control with "observation only," 24 weeks

Publication angle

"Benign" epilepsy is not actually benign — evidence from the past decade repeatedly shows clear language and executive-function impairment in this population, and international classification has already dropped the word "benign." These children have few seizures, follow up on a regular schedule, and parental anxiety is entirely focused on academics — a textbook case of high need plus zero available means

The EEG discharge index is recorded only as an observational marker and must not be used as a basis for judging efficacy or in any external claims.

Population

Ages 4–14, EEG discharges markedly improved and condition stable for 3+ months after steroid, immunoglobulin, or ASM treatment, but with residual cognitive, language, or behavioral regression. n=15–30 (a rare population; multi-site pooling recommended)

Primary endpoint

24-week Wechsler intelligence scale for children (or brief form) verbal comprehension and full-scale IQ + BRIEF

Secondary endpoints

Language function assessment, adaptive behavior scale (Vineland/ABAS), school reintegration and learning status, sleep, caregiver burden

Safety endpoints (important)

Seizure frequency, EEG discharge index, changes to immunotherapy and ASM regimen, adverse events

Design

Prospective cohort + parallel control (control being contemporaneous routine follow-up patients), 24–48 weeks

Publication angle

Cognitive regression from epileptic encephalopathy is one of the heaviest clinical burdens in pediatric neurology, and after the acute phase there is almost no intervention research targeting "recovery-phase cognitive rebuilding". Any single site has few cases, but every major center has an accumulated backlog, making this a natural theme for multi-site pooling

This direction must never delay or replace first-line treatment such as steroids or immunoglobulin; the enrollment point must be set after acute-phase treatment concludes. We recommend the protocol be jointly reviewed by our medical department and an epilepsy specialty center.

Population

Ages 6–18, confirmed autoimmune encephalitis, acute-phase immunotherapy completed, mRS ≤3 and condition stable for 1+ month, with residual cognitive, attention, or fatigue symptoms. n=20–40

Primary endpoint

24-week composite cognitive score (brief Wechsler form) + BRIEF executive function

Secondary endpoints

mRS and CASE score, PedsQL Multidimensional Fatigue Scale, school reintegration rate and post-return adjustment, academic performance

Safety endpoints (important)

Relapse events, changes to immunotherapy regimen and steroid dose, infection events, growth and development, adverse events

Design

Prospective cohort + parallel control, 24 weeks (extending cohort follow-up to 12 months is recommended)

Publication angle

Acute-phase treatment for pediatric autoimmune encephalitis already has consensus, but the recovery phase often lasts 1–2 years, sequelae are the family's greatest source of distress, and clinically there is essentially "nothing to offer" at this stage. Major domestic centers have a sizeable case volume, yet recovery-phase intervention research is nearly a blank slate

Division of labor with K8: K7 covers cognition and executive function (No. 3), K8 covers psychiatric/behavioral symptoms and sleep-wake rhythm disruption (No. 2); the same cohort can collect both endpoint sets in parallel. The protocol must state that this intervention neither affects nor replaces immunotherapy, with relapse as the top-priority safety event and pre-specified discontinuation/withdrawal rules.

Population

Ages 6–18, autoimmune encephalitis with acute-phase immunotherapy completed and condition stable for 1+ month, with residual irritability, mood instability, stereotyped behavior, or day-night reversal. n=20–40

Primary endpoint

12–24-week CBCL Externalizing behavior subscale + CSHQ sleep total score

Secondary endpoints

Sleep-wake rhythm records (sleep diary or actigraphy), ABC Irritability subscale, changes in antipsychotic and sedative-hypnotic dosing, mRS, caregiver burden and sleep

Safety endpoints (important)

Relapse events, changes to immunotherapy and psychiatric medication regimen, metabolic indicators (for those on long-term antipsychotics), adverse events

Design

Prospective cohort + parallel control, 24 weeks

Publication angle

What actually torments families in the recovery phase of anti-NMDAR encephalitis is often not cognition but behavioral disruption and reversed day-night rhythm — and at this stage, clinicians have little choice but to rely on antipsychotics and sedatives, with dose reduction extremely difficult. Setting "psychiatric medication dose reduction" as a secondary endpoint is more persuasive than any rating scale

Population

Ages 3–16, 1+ month past the acute phase, with residual consciousness, cognitive, motor, or behavioral impairment, receiving systematic rehabilitation training (including those fed via nasogastric tube). n=30–50

Primary endpoint

24-week WeeFIM (or GMFM-66, depending on the primary impairment type)

Secondary endpoints

Cognitive/developmental scale (brief Wechsler form or Gesell), effective participation time per training session (stopwatch-timed by the therapist), alertness, CSHQ sleep, caregiver burden

Safety endpoints (important)

Seizures, tube-feeding tolerance and aspiration events, growth curve, infection, adverse events

Design

Parallel control with "rehabilitation training only," 24 weeks

Publication angle

Encephalitis sequelae are a leading cause of acquired pediatric disability domestically; the recovery period is long, the assessment framework is already established, and follow-up attrition is near zero. Because No. 5 can be given via nasal tube, it is the only product line that can enter the pediatric critical-care and tube-feeding pathway — other functional foods cannot reach this channel

Pediatric dosing must follow physician instructions and be fixed in advance in the protocol. Tube administration requires defined preparation and flushing procedures, with tolerance recorded at every feeding.

Population

Ages 3–16, disorders of consciousness (VS/MCS) from encephalitis, hypoxic-ischemic injury, trauma, or post-surgery, condition stable for 4+ weeks, mostly tube-fed. n=15–30

Primary endpoint

24-week change in CRS-R total score and consciousness-state outcome (VS→MCS→emergence from MCS)

Secondary endpoints

Daily wakefulness time log, time available for rehabilitation training, complication rate, family burden and psychological state

Safety endpoints (important)

Tube-feeding tolerance, aspiration and aspiration pneumonia, seizures, infection, growth and development, adverse events

Design

Prospective single-arm, or parallel control with "standard arousal-focused rehabilitation only," 24 weeks

Publication angle

Arousal-support options for pediatric DOC are extremely limited, and nutrition/functional-food research in this space is nearly a blank slate. CRS-R is an internationally accepted endpoint, and a well-designed case series alone can be publishable

The direction on this list requiring the greatest ethical care: subjects cannot express consent themselves, so a guardian must sign and an independent safety monitoring structure is required. We recommend prioritizing sites with existing experience in pediatric DOC arousal support, with the protocol jointly reviewed by our medical department.

Population

Ages 6–16, 1–6 months after moderate-to-severe TBI, vital signs stable, with cognitive, fatigue, irritability, or sleep problems. n=30–50

Primary endpoint

12–24-week BRIEF executive function + PedsQL Multidimensional Fatigue Scale

Secondary endpoints

Brief Wechsler processing speed and working memory, CBCL behavior, CSHQ sleep, WeeFIM, school reintegration rate and post-return adjustment

Safety endpoints (important)

Post-traumatic seizures, worsening headache, abnormal imaging follow-up, adverse events

Design

Open-label pre/post control, or parallel control with "rehabilitation training only," 12–24 weeks

Publication angle

Fatigue and executive-function impairment after pediatric TBI are the leading cause of failed school reintegration. Adult TBI has an extensive literature, but pediatric data are severely lacking. This pairs with S10 (rehabilitation after TBI/neurosurgery) to form an adult–pediatric matched pair; cross-department coordination within the same hospital can share a common protocol and assessment set

Population

Ages 4–16, 1–6 months after moyamoya disease revascularization surgery, or 1–6 months after pediatric arterial ischemic stroke, condition stable and undergoing rehabilitation. n=20–40

Primary endpoint

24-week brief Wechsler composite cognitive score + PedsQL quality of life

Secondary endpoints

BRIEF executive function, WeeFIM/GMFM, PedsQL Multidimensional Fatigue Scale, school reintegration status, caregiver burden

Safety endpoints (important)

New stroke or TIA events, seizures, imaging/perfusion follow-up, adverse events

Design

Prospective cohort + parallel control, 24 weeks

Publication angle

Japan performs a large volume of pediatric moyamoya surgery, yet post-surgical cognitive follow-up data are extremely scarce — "how much cognition recovers after surgery" is what parents care about most and what almost no one has answered. A cohort like this has independent publication value on its own

New cerebrovascular events are the top-priority safety endpoint, with withdrawal and reporting rules set jointly with neurosurgery. Imaging follow-up should proceed per the existing clinical protocol and not be altered for the study.

Population

Ages 8–16, meeting ICHD-3 migraine criteria, with a 4-week baseline headache diary confirming ≥4 headache days per month; preventive treatment regimen stable for 4+ weeks or no preventive medication in use. n=40–60

Primary endpoint

12-week PedMIDAS pediatric migraine disability score + CSHQ sleep total score

Secondary endpoints

Monthly headache days and acute-medication use days (headache diary), SCARED/DSRS-C mood, BRIEF attention and executive function, school absence days, PedsQL

Safety endpoints

Headache-worsening events, acute-medication overuse, adverse events

Design

4-week baseline diary + 12-week open-label pre/post control, or randomized control (against standard headache-hygiene education)

Publication angle

The evidence base for preventive pharmacotherapy in pediatric migraine is itself thin — large randomized trials have shown amitriptyline and topiramate no better than placebo, so guidelines increasingly emphasize non-pharmacological and lifestyle management, which makes an "adjunct support" positioning especially legitimate. Meanwhile, sleep, anxiety, and attention comorbidities are extremely common in pediatric migraine yet rarely treated as endpoints

The primary endpoint is deliberately not set on headache days, but on disability and comorbidity burden, with headache days recorded only as a secondary endpoint. This preserves the compliance boundary of not claiming analgesic/preventive efficacy as a food product, while also aligning with the international trend toward "function as endpoint."

Population

Ages 3–14 with cerebral palsy (any GMFCS level I–V), CSHQ ≥41 or parent-reported night waking ≥3 nights/week; spasticity and pain management regimen stable for 4+ weeks. n=30–50

Primary endpoint

12-week CSHQ total score (or SDSC Sleep Disturbance Scale for Children)

Secondary endpoints

Sleep diary (sleep-onset latency, number and duration of night wakings), daytime behavior and training engagement, pain score, primary caregiver PSQI and ZBI

Safety endpoints

Seizures (comorbid epilepsy rate is high in cerebral palsy), feeding and bowel function, growth and development, adverse events

Design

Open-label pre/post control, or randomized control (against sleep-hygiene education), 12 weeks

Publication angle

Sleep problems are extremely common in children with cerebral palsy, yet options beyond melatonin are essentially absent; and it is the caregiver who is truly worn down by the night wakings. Making caregiver sleep a shared endpoint is a well-received angle for interdisciplinary rehabilitation/nursing journals. The division of labor with D12 is clean: D12 addresses daytime training tolerance, this direction addresses the night

Population

Ages 8–18, narcolepsy (type 1/2) or idiopathic hypersomnia confirmed by polysomnography and MSLT, medication regimen stable for 8+ weeks with residual daytime sleepiness. n=15–30

Primary endpoint

12-week ESS-CHAD (Epworth Sleepiness Scale for Children and Adolescents)

Secondary endpoints

Multi-timepoint KSS wakefulness self-rating, in-class sleepiness and absence days, BRIEF, mood, weight change

Safety endpoints (important)

Cataplexy frequency, primary-medication dose changes, cardiovascular adverse events, adverse events

Design

Open-label self-controlled pre/post, 12 weeks

Publication angle

Diagnosis of pediatric narcolepsy is commonly delayed, medication choice is age-restricted with notable side effects, and there is essentially no supplementary option for residual sleepiness. Arousal support is No. 5's core use case, but this direction must be led by a sleep center

Any suggestion that this could replace medications such as modafinil or sodium oxybate is strictly prohibited in any form; the protocol must specify that the primary medication is neither reduced nor discontinued during the study period.

Population

Ages 6–16 with a confirmed neuromuscular disease (primarily DMD), glucocorticoid regimen stable for 3+ months, receiving regular rehabilitation training. n=20–40

Primary endpoint

12–24-week PedsQL Neuromuscular Module fatigue domain + effective participation time per training session (therapist-recorded)

Secondary endpoints

BRIEF executive function and attention, 6-minute walk distance or NSAA (depending on disease stage), CSHQ sleep, academics and mood

Safety endpoints (important)

Weight and body-composition change (steroid-treated population), cardiopulmonary follow-up, fall events, adverse events

Design

Open-label pre/post control, 12–24 weeks

Publication angle

Cognitive and behavioral comorbidity in DMD has long been overlooked (linked to dystrophin isoform expression in the brain), while fatigue directly caps how much rehabilitation training a child can tolerate. Rare-disease parent communities are highly organized, so enrollment and follow-up are actually smoother than for more common conditions

State explicitly that motor function or disease-course change is not the primary endpoint. Weight and metabolic changes in steroid-treated patients should be recorded separately to avoid attribution confusion.

Population

Ages 6–18, intracranial tumor (medulloblastoma, glioma, etc.) with surgery and/or chemoradiotherapy completed 6+ months prior, no active disease, with decreased attention, memory, or processing speed, or academic difficulty. n=30–50

Primary endpoint

24-week brief Wechsler processing speed and working memory index + BRIEF

Secondary endpoints

PedsQL Brain Tumor Module, PedsQL Multidimensional Fatigue Scale, CSHQ sleep, mood, school reintegration and academic performance

Safety endpoints (important)

Tumor follow-up imaging and relapse events, post-radiotherapy endocrine function, growth curve, adverse events

Design

Open-label pre/post control, or parallel control with "routine follow-up only," 24 weeks

Publication angle

Survival rates for pediatric brain tumors have improved substantially, making cognitive sequelae a central long-term outcome issue, yet intervention options remain scarce. This pairs with Domain O (oncology supportive care) as an adult–pediatric matched direction; pediatric oncology and neurosurgery already have an established follow-up infrastructure, so the marginal cost of data collection is very low

Enrollment only after oncology confirms no active disease. Imaging follow-up should proceed per the existing tumor follow-up protocol and not be altered for the study.

Population

Ages 4–16, with any chronic condition under regular pediatric neurology follow-up (epilepsy, cerebral palsy, encephalitis sequelae, chronic headache, neuromuscular disease, neurogenetic disease, etc.), primary-condition regimen stable for 3+ months, with SCARED/DSRS-C or CSHQ at or above the cutoff. n=60–100, stratified by primary condition

Primary endpoint

12-week composite mood score (SCARED + DSRS-C) and CSHQ sleep total score as co-primary endpoints

Secondary endpoints

QOLCE-55 or PedsQL quality of life, school attendance, BRIEF, PSI-SF parenting stress, CGI-I; subgroup analysis stratified by primary condition

Safety endpoints (important)

Primary-disease activity indicators (seizure frequency, relapse, headache days, etc., pre-specified per disease), primary-medication dose adjustments and blood levels, adverse events

Design

Prospective cohort + parallel control or randomized control, 12 weeks; direct connection to the X1 multi-site unified registry is recommended

Publication angle

The fastest-recruiting direction in this domain — disease-agnostic, since pediatric neurology clinics generate eligible cases every day. Mood and sleep comorbidity is a burden shared across every chronic neurological condition, yet it has always been sliced up by disease and never handled together. The cross-disease design is itself a methodological selling point, and stratified analysis can yield multiple subgroup conclusions at once

Being cross-disease means safety endpoints must be pre-specified separately by disease; the protocol needs a disease-by-safety-indicator matrix, and cannot simply state "worsening of the primary disease." This is the key to whether this direction can clear ethics review.

Population

Ages 18–60, MDD, antidepressant stable for 8+ weeks, HAMD-17 ≤10 (clinical remission or partial remission), but with a subjective cognitive complaint (PDQ-5-D above cutoff). n=50–80

Primary endpoint

12-week change in THINC-it composite score or DSST (Digit Symbol Substitution Test)

Secondary endpoints

PDQ-5-D subjective cognition, TMT-A/B, HAMD-17, SDS functional impairment scale, return-to-work/school status

Design

Randomized double-blind placebo-controlled (first choice) or open-label control, 12 weeks

Publication angle

Residual cognitive symptoms are an international hot topic (CANTAB/THINC-it have become standard tools), and domestic non-pharmacological intervention data are extremely scarce. The subjective-objective cognition divergence is an analytical angle that readily yields findings

Population

Ages 18–60, MDD, antidepressant stable for 8+ weeks, HAMD shows partial remission but with prominent "no interest, no motivation, no energy," AES ≥34 or SHAPS suggesting anhedonia. n=40–60

Primary endpoint

AES Apathy Evaluation Scale or SHAPS anhedonia scale

Secondary endpoints

TEPS anticipatory/consummatory pleasure, Behavioral Activation for Depression Scale (BADS), HAMD (adjusted as covariate), SDS functional impairment, return-to-work/school status

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

Anhedonia and reduced motivation are the dimensions of depression least overcome by antidepressants (SSRIs may even worsen them), and they directly contribute to incomplete functional recovery. Framing "apathy improvement as independent of mood-symptom improvement" as the analytic core adds academic weight

Population

Ages 18–55, MDD, on SSRI treatment with mood symptoms in remission, but reporting "my emotions feel flat, I don't feel happy or sad, nothing matters anymore." n=40–60

Primary endpoint

OQESA (Oxford Questionnaire on the Emotional Side-effects of Antidepressants)

Secondary endpoints

AES apathy, SHAPS, sexual function and other SSRI side effects, self-directed SSRI discontinuation rate and adherence, HAMD (confirming no worsening)

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

This is a significantly underrecognized clinical problem — reported rates of emotional blunting reach 40–60%, making it one of the top reasons patients self-discontinue medication, yet effective interventions are almost nonexistent. Making "discontinuation rate" a shared primary endpoint directly links symptom improvement to relapse prevention. Domestic research is nearly a blank slate, and personally I consider this one of the directions on this list with the greatest potential to draw sudden attention

Population

After MDD treatment, HAMD in remission but with prominent fatigue/low energy. n=40–60

Primary endpoint

FSS fatigue severity or MFI-20

Secondary endpoints

PHQ-15, SDS function, work productivity (WPAI)

Design

Open-label pre/post control, 12 weeks

Publication angle

Fatigue is the most common yet least-measured residual symptom, and it is directly linked to relapse risk

Population

Patients on strongly sedating antidepressants such as mirtazapine, paroxetine, or trazodone, reporting daytime fatigue and grogginess. n=40–60

Primary endpoint

FSS fatigue severity or MFI-20

Secondary endpoints

ESS sleepiness, daytime function (WPAI work efficiency), rate of antidepressant dose reduction or switching, HAMD (confirming no worsening), medication adherence

Design

Open-label pre/post control, 12 weeks

Publication angle

Drug-induced fatigue is a classic scenario of "the illness resolved but life fell apart," and it is also a leading cause of medication switching or discontinuation. The framing of managing an adverse drug reaction is logically clean and ethically simple

Positioning of this domain: This is the domain with the deepest data accumulation among Japan-originated products, and it is also the easiest domain to enroll from in domestic memory clinics. We recommend emphasizing both ends of the spectrum — early stage (SCD/MCI) and BPSD/caregiver burden — as the two main thrusts: the former offers large sample sizes and fast recruitment, the latter presents the sharpest clinical challenge.

Population

Ages 18–65, MDD with insomnia, ISI ≥15, stable antidepressant regimen. n=40–60

Primary endpoint

ISI Insomnia Severity Index

Secondary endpoints

PSQI, sleep diary, change in sleep medication (including benzodiazepines/Z-drugs) use, HAMD sleep factor, daytime fatigue

Design

Open-label pre/post control or randomized control, 8–12 weeks

Publication angle

Set "sleep medication tapering" as a shared primary endpoint — de-benzodiazepine efforts are a current direction in both domestic policy and clinical practice, and this framing substantially raises the value of the paper

Population

Ages 12–18, MDD, within 7 days of starting an SSRI. n=50–80

Primary endpoint

HAMD/CDI change trajectory over the first 6 weeks, and "time to onset of effect"

Secondary endpoints

ARI irritability, agitation/restlessness, sleep, NSSI behavior frequency, early SSRI discontinuation rate

Safety endpoints

Activation syndrome and change in suicidal ideation (C-SSRS) must be monitored throughout

Design

Randomized control (SSRI + Chienomoto vs. SSRI), 6–12 weeks

Publication angle

The window before an SSRI takes effect is the period of highest risk in adolescent depression, and also the period with the highest attrition — yet intervention research here is nearly absent

Notes

Because this population carries suicide risk, ethical requirements are high; we recommend limiting this direction to sites with adolescent psychiatric wards and crisis-response protocols

Population

Ages 12–18 with NSSI behavior, on standard treatment. n=30–50

Primary endpoint

NSSI behavior frequency (self-injury log / OSI)

Secondary endpoints

DERS Difficulties in Emotion Regulation Scale, ARI irritability, impulsivity (BIS-11), sleep

Design

Open-label pre/post control, 12 weeks

Publication angle

NSSI is currently one of the most closely watched topics in adolescent psychology, and an emotion-regulation-mechanism angle offers more depth than a purely symptom-based angle

Notes

This is a high-risk population, so requirements for ethics and safety-response protocols are high

Population

Ages 18–55, BD-I/II in remission (YMRS ≤7 and HAMD ≤8 sustained for 8+ weeks), stable mood-stabilizer regimen. n=40–60

Primary endpoint

24-week change in cognition (brief MCCB, or digit symbol + TMT + verbal fluency)

Secondary endpoints

BRIAN circadian rhythm scale, PSQI, FAST functioning assessment, quality of life

Safety endpoints (important)

YMRS and ASRM must be monitored throughout for manic-switch risk, with mood episodes logged individually

Design

Open-label pre/post control, 24 weeks (cognitive endpoints require longer observation)

Publication angle

Cognitive impairment during bipolar remission is central to incomplete functional recovery, with no effective medication available. In addition, safety data showing that "a supplementary supplement does not trigger manic switching" has independent value on its own

Notes

Manic-switch risk is the single greatest scientific and compliance risk in this direction, and the protocol must include clear discontinuation criteria

Population

Depressive disorder in patients age 60+, GDS-15 ≥8, MoCA 18–25 (suggesting mild cognitive impairment), stable antidepressant regimen. n=40–60

Primary endpoint

Dual endpoint of MoCA + GDS-15

Secondary endpoints

AVLT auditory verbal learning, daily function (IADL), sleep, fall events

Design

Open-label pre/post control, 24 weeks

Publication angle

Late-onset depression is a prodromal symptom of dementia, and the intervention window for the "depression-dementia continuum" is a recently prominent theme. Publishable from geriatrics, psychiatry, or neurology alike

Population

Ages 18–65, GAD or anxiety disorder, HAMA ≥14, stable regimen. n=40–60

Primary endpoint

HAMA total score (separable into somatic and psychic factors)

Secondary endpoints

GAD-7, PHQ-15 somatization, PSQI, change in benzodiazepine use

Design

Open-label pre/post control, 8–12 weeks

Publication angle

The somatic subtype of anxiety responds poorly to medication and is seen across scattered departments (gastroenterology, cardiology), making it an underrecognized population

Population

Depression patients undergoing an rTMS course or MECT. n=30–50

Primary endpoint

HAMD response rate at end of course / post-MECT cognitive recovery (MMSE, AVLT)

Secondary endpoints

Treatment-related adverse events (headache, memory impairment), sleep, course completion rate

Design

Randomized control, covering the full course + 4 weeks of follow-up

Publication angle

Nutritional protection against post-MECT cognitive impairment is a very novel angle, with very few people working on it domestically

Population

Age 55+, memory complaints with normal objective cognition (MoCA ≥26, CDR=0). n=60–100

Primary endpoint

SCD-Q / MAC-Q subjective cognitive questionnaire; objective memory (AVLT) as a shared endpoint

Secondary endpoints

HADS anxiety/depression, sleep, quality of life, cognition-related healthcare-seeking behavior

Design

Randomized control (control arm receives health education), 24 weeks

Publication angle

SCD is the largest and least-studied population in memory clinics, with enrollment speed far exceeding MCI/AD. The "subjective-objective divergence" analysis carries theoretical depth

Population

Age 55+, meets Petersen MCI criteria, MoCA 18–25, CDR=0.5. n=50–80

Primary endpoint

24-week change in ADAS-Cog or MoCA

Secondary endpoints

AVLT delayed recall, TMT, daily function (FAQ), mood, sleep, conversion rate to dementia (long-term follow-up)

Design

Randomized control (open-label or double-blind), 24 weeks. Extended follow-up to 12 months is recommended

Publication angle

MCI intervention is a global hot topic. If the cohort can be retained through a 12-month conversion-rate follow-up, the value doubles

Population

Mild-to-moderate AD, donepezil/memantine stable for 3+ months, MMSE 10–24. n=40–60

Primary endpoint

ADAS-Cog (or MMSE)

Secondary endpoints

ADCS-ADL activities of daily living, NPI-Q, CDR-SB, caregiver burden (ZBI)

Design

Open-label self-controlled pre/post or parallel control, 24 weeks

Publication angle

Cognitive endpoints in AD rarely show significant change within 24 weeks, so we recommend setting ADL and NPI as shared primary endpoints — both success probability and clinical significance are higher

Population

Various dementias with BPSD, NPI-Q total score ≥6 or a prominent agitation subscale. n=40–60

Primary endpoint

NPI-Q total score and agitation/irritability subscale

Secondary endpoints

CMAI agitation inventory, change in antipsychotic dose, caregiver burden (ZBI), risk of institutionalization

Design

Open-label pre/post control, 12 weeks

Publication angle

BPSD is the most distressing challenge in dementia care, and antipsychotics carry a black-box warning, with guidelines emphasizing non-pharmacological approaches first. Demonstrating "antipsychotic dose reduction" would be a very strong selling point for the paper

Population

Mild-to-moderate AD, VCI, or PDD, prominent NPI apathy subscale or AES-I (caregiver form) ≥38, stable cholinesterase inhibitor regimen. n=40–60

Primary endpoint

AES-I Apathy Evaluation Scale (caregiver form) or NPI apathy subscale

Secondary endpoints

Engagement in daily activities (caregiver activity diary), ADCS-ADL, cognition (MoCA/ADAS-Cog), depression (CSDD Cornell Scale for Depression in Dementia, for differentiation), ZBI caregiver burden

Design

Open-label pre/post control, 12–24 weeks

Publication angle

Apathy is the most prevalent BPSD in dementia (50–70%), higher than agitation, yet one of the least studied — because it is "quiet," families rarely complain about it, and physicians rarely prescribe for it. Yet it directly determines whether a patient can engage in activities, socializing, and rehabilitation, and it is the deepest source of caregiver helplessness. Currently there is no approved treatment. This direction carries extremely high clinical value with very little competition

Population

Dementia with nighttime awakening, day-night reversal, or evening agitation. n=30–50

Primary endpoint

Sleep diary (caregiver-recorded) total sleep time and number of night wakings; or actigraphy rhythm parameters

Secondary endpoints

Frequency of sundowning episodes, NPI nighttime behavior subscale, caregiver sleep and burden, sleep medication use

Design

Open-label pre/post control, 8–12 weeks

Publication angle

Sundowning directly determines whether a family can sustain home care and is the leading trigger for institutionalization, giving it extremely high clinical significance

Population

Probable DLB, stable regimen. n=20–40 (case series acceptable given the rare-disease context)

Primary endpoint

NPI hallucination subscale + cognitive fluctuation scale (CAF / MFC)

Secondary endpoints

RBDSQ, MoCA, UPDRS-III, fall events, antipsychotic hypersensitivity events

Design

Open-label pre/post control or prospective case series, 12–24 weeks

Publication angle

DLB patients are highly sensitive to antipsychotics (risking neuroleptic malignant syndrome), leaving treatment options extremely limited. Even an n=20 case series has publication value

Population

PD with a cognitive complaint, MDS-criteria PD-MCI, stable anti-Parkinsonian regimen. n=40–60

Primary endpoint

MoCA / PD-CRS Parkinson's Disease Cognitive Rating Scale

Secondary endpoints

MDS-UPDRS-I (non-motor symptoms), RBDSQ, PDSS-2 sleep, depression, quality of life PDQ-39

Design

Open-label pre/post control, 24 weeks

Publication angle

Non-motor symptoms of PD (cognition, sleep, mood) are the current mainstream direction of PD research, leaving substantial room beyond motor symptoms

Population

VCIND or mild vascular dementia, 3+ months post-stroke, stable secondary-prevention regimen. n=40–60

Primary endpoint

MoCA + executive function (TMT-B, Stroop)

Secondary endpoints

Mood/apathy, depression, daily function, recurrence events

Design

Open-label pre/post control, 24 weeks

Publication angle

VCI is primarily driven by executive dysfunction (distinct from the memory impairment of AD); choosing the right cognitive assessment tool is key to success

Population

Behavioral-variant FTD. n=15–30

Primary endpoint

FBI Frontal Behavioral Inventory / NPI disinhibition and apathy subscales

Secondary endpoints

CBI-R, caregiver burden, cognition (frontal executive function)

Design

Prospective case series, 24 weeks

Publication angle

FTD has no approved treatment at all, and case series for rare diseases have a stable publication venue in specialty journals

Population

Community-dwelling or outpatient adults age 65+, FRAIL scale 1–3 (pre-frail/frail), with fatigue among the chief complaints. n=50–80

Primary endpoint

FRAIL scale score or Fried frailty phenotype classification

Secondary endpoints

Grip strength, 4m gait speed, SPPB Short Physical Performance Battery, FSS fatigue, MNA-SF nutrition, falls and hospitalization events, cognition and mood

Design

Randomized control (control arm receives exercise + nutrition counseling), 24 weeks

Publication angle

Fatigue is one of the five core criteria in the Fried frailty phenotype, and frailty is currently one of the most closely watched areas in geriatric medicine, directly linked to functional decline, hospitalization, and mortality. It can be led by geriatrics, general medicine, or rehabilitation medicine, and published in both geriatric-medicine and clinical-nutrition journals

Positioning of this domain: Psychiatric inpatient/day-care wards are the research setting with the highest medication adherence and follow-up completion (patients are concentrated, medication can be supervised, and attrition is extremely low). We recommend focusing on negative symptoms, cognitive impairment, and tapering of sedating medications as the main thrusts.

Population

Primary caregivers of moderate-to-severe dementia patients, ZBI ≥21. n=40–60

Primary endpoint

ZBI caregiver burden scale

Secondary endpoints

Caregiver PHQ-9, GAD-7, PSQI, quality of life, caregiver's own cognitive complaints

Design

Randomized control (control arm receives standard caregiving education), 12 weeks

Publication angle

High acceptance rates in nursing journals, with fast enrollment and good adherence. Can also be run as a parallel sub-study alongside the A4/A8 directions

Population

Ages 18–55, stable-phase schizophrenia, antipsychotic stable for 8+ weeks, PANSS negative scale ≥15. n=50–80

Primary endpoint

PANSS negative scale or SANS

Secondary endpoints

MCCB / BACS cognitive battery, PSP personal and social functioning, CGI-S, positive symptoms (safety observation)

Safety endpoints

Positive-symptom worsening events, hospitalization events

Design

Randomized control (open-label or double-blind), 12–24 weeks

Publication angle

Negative symptoms and cognitive impairment represent the greatest unmet need in schizophrenia, and are also central to social functioning. There is clear room for adjunct-intervention research in Japan

Population

Ages 18–55, stable-phase schizophrenia, antipsychotic stable for 8+ weeks, BNSS or CAINS showing prominent motivation-pleasure dimension impairment. n=40–60

Primary endpoint

BNSS Brief Negative Symptom Scale "motivation-pleasure" factor, or CAINS-MAP

Secondary endpoints

MAP-SR self-rated motivation and pleasure, daily activity log (behavioral measure), PSP social functioning, PANSS negative scale, cognition

Design

Randomized control, 12–24 weeks

Publication angle

Negative symptoms have already been clearly separated into two independent factors — "diminished expression" and "diminished motivation-pleasure" — with the latter more predictive of functional outcome and less responsive to medication. Using next-generation tools like BNSS/CAINS instead of PANSS-N as the primary endpoint itself demonstrates methodological sophistication

Population

Patients on strongly sedating antipsychotics such as quetiapine, clozapine, or olanzapine, with ESS ≥10 or reporting that daytime sleepiness affects functioning. n=40–60

Primary endpoint

ESS Epworth Sleepiness Scale

Secondary endpoints

FSS fatigue, daytime alertness (KSS at multiple time points), cognition (reaction time, sustained attention), self-directed antipsychotic discontinuation rate and adherence, PSP functioning, psychiatric symptoms (confirming no worsening)

Design

Randomized control, 12 weeks

Publication angle

Daytime sedation is the single biggest factor undermining antipsychotic adherence, and a direct barrier to returning to work and reintegrating socially. In clinical practice physicians usually have only two options: "switch medication or endure it." Making adherence a shared endpoint directly links it to relapse risk

Positioning of this domain: The subacute inpatient rehabilitation window (2 weeks to 3 months post-onset) in rehabilitation medicine is an ideal research setting — patients are hospitalized daily, assessment is completed routinely by therapists, and follow-up attrition is zero. We recommend prioritizing three directions with no effective medication: post-stroke cognition, fatigue, and apathy.

Population

Chronic patients hospitalized 1+ year, stable regimen. n=50–80

Primary endpoint

PANSS total score + PSP functioning

Secondary endpoints

Cognition, sleep, independence in daily living, nurse observation scale (NOSIE), weight and metabolic markers

Design

Randomized control, 24 weeks

Publication angle

The most feasible direction overall — medication can be supervised, follow-up attrition is zero, assessment is performed by ward nurses, and there is no risk of losing patients to follow-up. Well suited as a first joint project with a psychiatric specialty hospital

Population

First episode, within 3 months of starting an antipsychotic, ages 18–35. n=40–60

Primary endpoint

24-week change in the MCCB cognitive battery

Secondary endpoints

PANSS, PSP, return-to-school/work rate, correlation analysis with DUP

Design

Randomized control, 24 weeks

Publication angle

The "cognitive trajectory" during the first episode is a central theme of early-intervention research worldwide

Population

Hospitalized psychiatric patients on long-term benzodiazepine or Z-drug hypnotics, with intent to taper. n=40–60

Primary endpoint

Reduction in benzodiazepine daily equivalent dose (diazepam equivalent)

Secondary endpoints

PSQI, ISI, tapering success rate, withdrawal-related symptoms, fall events, daytime sleepiness

Design

Randomized control (standard tapering protocol ± Chienomoto), 12 weeks

Publication angle

De-benzodiazepine efforts are a shared policy direction domestically and internationally, and linking an adjunct approach to tapering success rate is one of the strongest publication concepts on this list. Correlation analysis with fall risk in elderly patients adds further points

Population

OCD with residual symptoms despite adequate SSRI dose and duration, Y-BOCS ≥16. n=30–50

Primary endpoint

Y-BOCS total score

Secondary endpoints

Anxiety/depression, sleep, function, quality of life

Design

Open-label pre/post control, 12 weeks

Publication angle

OCD has a low response rate and high residual-symptom rate, yet adjunct-intervention research is limited

Population

Closed-ward psychiatric patients. n=50–100

Primary endpoint

Nighttime adverse-event rate (falls, impulsive behavior, frequency of physical restraint use)

Secondary endpoints

NOSIE nurse observation scale, nursing workload records, patient sleep

Design

Pre/post control (ward level) or randomized control, 12 weeks

Publication angle

Led by the nursing team with little competition, and high acceptance rates in core nursing journals. Data come from routine ward records, so collection cost is nearly zero

Population

2 weeks–6 months after first stroke, MoCA <26, receiving cognitive rehabilitation training. n=50–80

Primary endpoint

12–24 week change in MoCA or LOTCA

Secondary endpoints

Executive function (TMT-B, Stroop), AVLT, MBI activities of daily living, mRS

Design

Randomized control (standard rehabilitation ± Chienomoto), 12–24 weeks

Publication angle

PSCI occurs in 30–60% of patients, yet guideline recommendations remain weak, making it the most mainstream research direction in rehabilitation medicine

Population

1–6 months post-stroke, HAMD-17 ≥8 or PHQ-9 ≥5. n=40–60

Primary endpoint

HAMD-17 or PHQ-9

Secondary endpoints

Engagement and cooperation with rehabilitation training, MBI, fatigue, sleep, rate of antidepressant initiation

Design

Randomized control, 12 weeks

Publication angle

PSD directly affects adherence to rehabilitation training. Setting "training engagement" as a secondary endpoint links mood improvement to functional recovery, making the logic more complete

Population

1+ months post-stroke, FSS ≥4 or FAS ≥22. n=40–60

Primary endpoint

FSS Fatigue Severity Scale

Secondary endpoints

Rehabilitation training tolerance time (objective measure), 6-minute walk distance, mood, sleep, quality of life

Design

Randomized control, 12 weeks

Publication angle

No effective medication currently exists for post-stroke fatigue, and guidelines can only recommend non-pharmacological approaches — one of the most "legitimately justified" indication scenarios for a functional food

Population

1–6 months post-stroke, AES suggesting apathy, requiring differentiation from depression. n=30–50

Primary endpoint

AES Apathy Evaluation Scale

Secondary endpoints

Proactivity in rehabilitation training (therapist-rated), executive function, MBI, family burden

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

Separating apathy from depression is a recently prominent theme, with very little domestic research. Apathy is the largest hidden barrier to rehabilitation training, and resonates strongly with clinicians

Population

2 weeks–6 months post-stroke, ESS ≥10 or frequent sleepiness/reduced alertness during rehabilitation training (more common with thalamic, brainstem, or frontal lesions). n=40–60

Primary endpoint

ESS Epworth Sleepiness Scale

Secondary endpoints

Alertness during rehabilitation sessions (KSS at multiple pre/post time points), effective training time, MoCA, AES apathy (for differentiation), PSQI (to rule out night-sleep deficit), MBI

Design

Randomized control, 12 weeks

Publication angle

Post-stroke sleepiness directly eats into effective rehabilitation training time, yet it has almost never been studied as a standalone endpoint. Together with S3 fatigue and S4 apathy, it forms a "hypoarousal triad" — the three directions can run in parallel within the same department and share an assessment framework

Positioning of this domain: This is the domain with the least competition, the fastest recruitment, and the lowest ethical risk. The core angle is "people who do not want, or are not suited for, menopausal hormone therapy (MHT)" — a population that gynecology clinics face daily without a solution to offer.

Population

Post-stroke insomnia or disrupted sleep architecture, PSQI >7. n=40–60

Primary endpoint

PSQI / ISI

Secondary endpoints

Sleep diary, sleep medication use, daytime rehabilitation training performance, fatigue, cognition

Design

Randomized control, 8–12 weeks

Publication angle

Post-stroke sleep disorder affects neuroplasticity and functional recovery, giving a complete mechanistic narrative

Population

Inpatient rehabilitation patients 2 weeks–3 months post-stroke, regardless of specific symptoms. n=60–100

Primary endpoint

Composite symptom burden (combined score of cognition MoCA + mood HADS + fatigue FSS + sleep PSQI)

Secondary endpoints

FMA motor function, MBI, length of stay, discharge mRS

Design

Randomized control, covering the full inpatient rehabilitation period (typically 4–12 weeks)

Publication angle

Closely matches real-world clinical practice, with the lowest enrollment and follow-up cost. Symptom-cluster analysis is a current methodological trend in rehabilitation research

Population

Post-stroke aphasia, receiving systematic speech therapy. n=30–50

Primary endpoint

WAB Western Aphasia Battery, Aphasia Quotient (AQ)

Secondary endpoints

CADL communication ability, mood, family communication burden

Design

Randomized control, 12 weeks

Publication angle

Because aphasia rehabilitation assessment is time-consuming, we recommend limiting this direction to sites with dedicated speech-language pathologists

Population

Stroke patients age 65+, MNA-SF suggesting nutritional risk. n=40–60

Primary endpoint

MNA nutrition assessment + grip strength/skeletal muscle index

Secondary endpoints

Albumin/prealbumin, MBI, infectious complications, length of stay

Design

Randomized control, 12 weeks

Publication angle

The interdisciplinary nutrition-rehabilitation angle is publishable in clinical-nutrition journals. This draws a different author group than rehabilitation medicine and can run in parallel

Population

Mild-to-moderate TBI or 1–6 months after craniotomy, stable condition. n=30–50

Primary endpoint

MoCA + executive function

Secondary endpoints

Post-concussion symptom scale (RPQ), mood, sleep, fatigue, return-to-work rate

Design

Open-label pre/post control or randomized control, 12–24 weeks

Publication angle

Post-TBI syndrome has long lacked intervention options, and can be led by either neurosurgery or rehabilitation medicine

Population

Women ages 40–58 in perimenopause/early menopause, modified Kupperman score ≥15, not using MHT. n=50–80

Primary endpoint

Modified Kupperman score or MRS Menopause Rating Scale

Secondary endpoints

Hot flash frequency/severity diary, PSQI, HADS, MENQOL quality of life

Design

Randomized control (control arm receives lifestyle counseling), 12 weeks

Publication angle

Fast enrollment and low attrition, with assessment completed by scales alone. The lowest-cost direction to launch on this entire list

Population

Women with moderate-to-severe symptoms who have an MHT contraindication (history of thrombosis, liver disease, unexplained genital bleeding, etc.) or clearly decline MHT. n=50–80

Primary endpoint

Modified Kupperman / MRS

Secondary endpoints

Hot flash diary, sleep, mood, quality of life, satisfaction with and intent to continue the intervention

Design

Randomized control or single-arm pre/post control, 12 weeks

Publication angle

The most clearly defined clinical gap population — guidelines explicitly note that no effective alternative exists for these patients, so the "clinical need" section of the paper practically writes itself

Population

Women on standard MHT for 3+ months who still have residual symptoms (especially mood, sleep, cognition). n=40–60

Primary endpoint

Severity of residual symptoms (by Kupperman item)

Secondary endpoints

Sleep, mood, cognition, change in MHT dose, MHT adherence

Design

Open-label pre/post control, 12 weeks

Publication angle

MHT is highly effective for vasomotor symptoms, but its effect on mood and cognition is limited — this "efficacy gap" is precisely the rationale for add-on therapy

Population

Perimenopausal women with mild-to-moderate HADS or PHQ-9/GAD-7, not meeting criteria for major depression. n=40–60

Primary endpoint

HADS or PHQ-9 + GAD-7

Secondary endpoints

Kupperman mood-related items, sleep, irritability, self-rated impact on family and work

Design

Randomized control, 12 weeks

Publication angle

Whether to use antidepressants for perimenopausal depression is a clinical point of debate, and there is clear room for non-pharmacological intervention in this borderline population

Population

Perimenopausal women, PSQI >7 or ISI ≥15. n=40–60

Primary endpoint

PSQI / ISI

Secondary endpoints

Correlation analysis of nighttime hot flashes and awakening, sleep diary, daytime fatigue, mood, sleep medication use

Design

Randomized control, 8–12 weeks

Publication angle

Correlation analysis linking nighttime hot flashes and sleep disruption is an interesting angle — distinguishing "sleep improvement driven by hot-flash improvement" from "independent sleep improvement"

Population

Perimenopausal women ages 40–58 reporting persistent fatigue for 3+ months, FSS ≥4, with correctable causes such as anemia or thyroid dysfunction excluded. n=50–80

Primary endpoint

FSS Fatigue Severity Scale or MFI-20 Multidimensional Fatigue Inventory

Secondary endpoints

Kupperman/MRS, PSQI (distinguishing "tiredness from poor sleep" from "independent fatigue"), HADS, MENQOL, work productivity (WPAI)

Design

Randomized control, 12 weeks

Publication angle

Fatigue is consistently among the top 3 chief complaints in perimenopause, yet it is rarely studied as a primary endpoint — in Kupperman it is just a single item. Making it a standalone primary endpoint gives the study an immediately recognizable identity. The requirement to exclude anemia/hypothyroidism also demonstrates methodological rigor

Population

Perimenopausal women reporting "I don't feel like doing anything, nothing interests me, I'm sleepy during the day," positive AES or ESS, with depression not meeting clinical diagnostic criteria. n=40–60

Primary endpoint

AES Apathy Evaluation Scale + ESS sleepiness scale

Secondary endpoints

SHAPS anhedonia, HADS (covariate adjustment), Kupperman, social activity participation, quality of life

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

In clinics, such complaints are often lumped together as "menopausal depression" and treated with antidepressants, but most do not actually meet the diagnostic criteria for depression. Separating "apathy" from "depression" is both an academic contribution and a direct answer to the physician's everyday dilemma of whether to prescribe

⚠️ Uniform compliance standard: In all oncology-direction protocols and papers, endpoints related to anti-tumor effect — such as tumor shrinkage rate, progression-free survival, or overall survival — must not be touched, and no claim of any kind regarding anti-tumor effect may be made. Endpoints must be strictly limited to symptom burden and quality of life. For safety, interactions with anti-tumor treatment must be recorded.

Population

Perimenopausal women with a memory/attention complaint but normal objective cognition. n=50–80

Primary endpoint

Subjective cognitive questionnaire (PDQ-5-D / Cognitive Failures Questionnaire, CFQ) + objective cognition (DSST, verbal fluency, working memory)

Secondary endpoints

Kupperman, mood, sleep, work productivity (WPAI)

Design

Randomized control, 12–24 weeks

Publication angle

"Menopausal brain fog" has been an international talking point in recent years, yet it is almost entirely unstudied domestically, giving it very high novelty. The estrogen-cognition hypothesis also provides theoretical grounding that makes the discussion section easier to write

Population

POI patients under age 40. n=30–50

Primary endpoint

MRS / MENQOL

Secondary endpoints

Mood, sleep, cognition, fertility-related psychological distress, social functioning

Design

Open-label pre/post control, 12–24 weeks

Publication angle

POI patients are young and carry a heavy psychological burden, yet follow-up adherence is very good — an overlooked, high-value population

Population

Breast or colorectal cancer, receiving or having just completed chemotherapy with a regimen containing anthracyclines/taxanes/oxaliplatin, with a cognitive complaint. n=50–80

Primary endpoint

FACT-Cog cognitive function scale (subjective) + objective cognition (DSST, TMT-B, AVLT)

Secondary endpoints

HADS, ISI, FACIT-F fatigue, quality of life EORTC QLQ-C30, return-to-work rate

Design

Randomized control, covering the chemotherapy period + 3 months of post-chemotherapy follow-up

Publication angle

CRCI is a front-line hot topic in international oncology supportive care, yet domestic data are extremely scarce. The subjective-objective cognition divergence analysis is a reliable bonus point in the discussion

Population

Solid tumor patients, BFI Brief Fatigue Inventory ≥4 or FACIT-F suggesting moderate-to-severe fatigue, with correctable causes such as anemia or hypothyroidism excluded. n=50–80

Primary endpoint

BFI or FACIT-F

Secondary endpoints

ECOG performance status, 6-minute walk, sleep, mood, chemotherapy completion rate and dose intensity

Design

Randomized control, 8–12 weeks

Publication angle

CRF has the highest prevalence (60–90%) of any symptom with no approved medication, and NCCN guidelines explicitly recommend non-pharmacological intervention — the single direction most aligned with Chienomoto's positioning. Setting "chemotherapy dose-intensity maintenance rate" as a secondary endpoint substantially raises clinical significance

Population

Solid tumor patients receiving curative-intent radiotherapy (breast, head and neck, or prostate cancer preferred), enrolled before radiotherapy begins. n=50–80

Primary endpoint

FACIT-F or BFI fatigue trajectory during radiotherapy and through 4 weeks after completion

Secondary endpoints

Timing and peak of fatigue onset, number of radiotherapy interruptions/delays, ECOG, sleep, mood, QLQ-C30

Design

Randomized control, the full radiotherapy course (typically 5–7 weeks) + 4 weeks of post-radiotherapy follow-up

Publication angle

The time course of radiation-related fatigue is highly predictable (typically onset in weeks 2–3, peaking at the end of the course). This means the enrollment point, observation window, and assessment time points are all naturally fixed, making this one of the cleanest designs with the lowest attrition among all fatigue studies. Since patients attend daily for radiotherapy, follow-up cost is near zero

Population

Solid tumor patients during or after treatment, AES ≥34 or ESS ≥10, reporting "I don't feel like doing anything, I'm sleepy all day," with the HADS depression item not reaching clinical diagnosis. n=40–60

Primary endpoint

AES Apathy Evaluation Scale + ESS sleepiness scale

Secondary endpoints

FACIT-F fatigue (for differentiation from fatigue), HADS (covariate adjustment), engagement in daily activities, QLQ-C30, family observational rating

Design

Open-label pre/post control, 12 weeks

Publication angle

Oncology supportive care almost exclusively discusses fatigue, while "apathy" remains largely untouched as an independent construct. Yet in practice, patients who are "bedbound with no will to do anything" are very common, and are often misidentified and treated as depression. A three-way separation analysis of fatigue-apathy-depression carries high novelty

Population

Cancer patients during or after treatment, ISI ≥15. n=40–60

Primary endpoint

ISI Insomnia Severity Index

Secondary endpoints

PSQI, sleep diary, sleep medication use, fatigue, mood, quality of life

Design

Randomized control, 8–12 weeks

Publication angle

Insomnia prevalence in cancer patients is 2–3 times that of the general population, and long-term benzodiazepine use risk is also elevated. The sleep-medication-tapering angle applies here as well

Population

Solid tumor patients within 6 months of confirmed diagnosis, Distress Thermometer (DT) ≥4 or HADS ≥8. n=50–80

Primary endpoint

HADS anxiety/depression subscales

Secondary endpoints

DT distress thermometer, sleep, fatigue, treatment adherence, QLQ-C30

Design

Randomized control, 12 weeks

Publication angle

Psycho-oncology is a distinct journal group with less competition than clinical oncology

Population

3+ months of tamoxifen or aromatase inhibitor therapy after breast cancer surgery, with hot flash, mood, sleep, or cognitive complaints. n=50–80

Primary endpoint

FACT-ES endocrine symptom subscale or modified Kupperman

Secondary endpoints

Hot flash diary, HADS, ISI, FACT-Cog, joint pain VAS, endocrine therapy adherence and discontinuation rate

Design

Randomized control, 12–24 weeks

Publication angle

"Adherence" is the trump-card endpoint for this direction — 30–50% of patients discontinue endocrine therapy within 5 years, and these symptoms are a leading cause. Linking symptom improvement to sustained adherence connects clinical significance directly to survival benefit

⚠️ Required pre-check

Because this direction involves a hormone-sensitive tumor, we must provide phytoestrogen/estrogen-like activity assessment data for the ingredients before enrollment begins, and this must be clearly explained in the protocol and informed consent. If the documentation is insufficient, this direction should be put on hold.

Population

Patients after meningioma or glioma surgery, or receiving whole-brain/local radiotherapy, stable condition. n=30–50

Primary endpoint

MoCA + HVLT-R Hopkins Verbal Learning Test (a standard tool in radiotherapy-cognition research)

Secondary endpoints

Executive function, fatigue, mood, seizure frequency, quality of life QLQ-BN20

Design

Randomized control or pre/post control, 24 weeks

Publication angle

Radiation-induced cognitive impairment is a clearly defined clinical challenge (memantine is currently the only medication with evidence), leaving substantial room. Can be co-led by neurosurgery and radiation oncology

Population

Solid tumor patients receiving PD-1/PD-L1 inhibitor therapy. n=40–60

Primary endpoint

FACIT-F fatigue

Secondary endpoints

QLQ-C30, sleep, mood, irAE records (safety)

Design

Open-label pre/post control, 12 weeks

Publication angle

Supportive-care research in the immunotherapy population is just beginning, giving it high novelty

⚠️ Notes

Immune-related adverse events must be clearly recorded, and the protocol must not include any language regarding immune modulation

Population

Primary caregivers of cancer patients in advanced-stage or active treatment, ZBI ≥21. n=40–60

Primary endpoint

ZBI caregiver burden

Secondary endpoints

Caregiver HADS, PSQI, quality of life, anticipatory grief (PG-12)

Design

Randomized control, 12 weeks

Publication angle

Cancer-caregiver research has a stable publication venue in nursing and psycho-oncology journals, and enrollment is extremely fast

Population

Patients requiring long-term nasogastric, nasojejunal, or gastrostomy feeding due to stroke, TBI, hypoxic encephalopathy, etc., stable for 2+ weeks. n=30–50

Primary endpoint

Composite feeding tolerability score (gastric residual volume, bloating, diarrhea, vomiting) + CRS-R Coma Recovery Scale-Revised or GCS

Secondary endpoints

Prealbumin, weight, mid-upper arm circumference, pneumonia incidence, engagement in rehabilitation training, caregiver assistance burden

Safety endpoints (important)

Aspiration events, tube blockage, GI adverse events — must be recorded individually

Design

Open-label pre/post control or randomized control, 12 weeks

Publication angle

Nasal-tube administration is a strength unique to Chienomoto for this population — most functional foods cannot enter the enteral-feeding route. Tube-fed patients are concentrated in neurology, post-ICU, and rehabilitation wards, so follow-up attrition is zero. In addition, "tube passability and tolerability" can itself become an independently publishable paper

Required pre-check: We must first provide data on the product's solubility, viscosity, and tube passability (including blockage risk across various tube diameters); without this, the direction cannot be designed. This carries the strictest prerequisites of any direction on the full list.

Population

Inpatients age 18+, NRS-2002 ≥3 (nutritional risk), FSS ≥4 or reporting overt fatigue, on a standard nutrition-support protocol. n=50–80

Primary endpoint

FSS Fatigue Severity Scale

Secondary endpoints

PG-SGA subjective global assessment, grip strength, albumin and prealbumin, daily oral intake, appetite score (SNAQ), length of stay

Design

Randomized control (standard nutrition support ± Chienomoto), 8–12 weeks

Publication angle

Nutritional risk and fatigue are mutually causal, yet "fatigue" is rarely made the primary endpoint of nutrition-intervention research. The assessment framework in clinical nutrition is already well established, and every measure here comes from data the department already collects in routine practice

Population

Age 65+, meeting AWGS 2019 sarcopenia diagnostic criteria, or FRAIL scale 1–3 (pre-frail to frail). n=50–80

Primary endpoint

Grip strength + 4m gait speed (or SPPB Short Physical Performance Battery)

Secondary endpoints

Skeletal muscle mass index (bioelectrical impedance), FSS fatigue, MNA-SF, falls and hospitalization events, cognition and mood

Design

Randomized control (control arm receives resistance exercise + nutrition counseling), 24 weeks

Publication angle

Sarcopenia and frailty are currently among the most closely watched areas in geriatric medicine, and fatigue is precisely one of the five core criteria in the Fried frailty phenotype. Clinical nutrition, geriatrics, and rehabilitation medicine can all lead this, and it is submittable to both clinical-nutrition and geriatric-medicine journals

This is a different angle on the same population as A11 in the geriatric dementia domain — clinical nutrition and geriatrics can each lead their own study while sharing the same subject pool.

Population

Age 65+ undergoing elective major surgery or hip-fracture surgery, preoperative MNA-SF suggesting nutritional risk or malnutrition. n=60–100

Primary endpoint

Postoperative delirium incidence (CAM or 3D-CAM, assessed daily on postoperative days 1–7)

Secondary endpoints

Postoperative cognition (MoCA at discharge and 3 months post-op), grip strength, length of stay, complication rate, 30-day readmission rate

Design

Randomized control, from 7 days preoperatively through 30 days postoperatively

Publication angle

Postoperative delirium after hip fracture occurs in 20–40% of older patients, and preventive options are limited. It is a hard outcome of shared interest to anesthesiology, geriatrics, and orthopedics alike. Nutritional intervention for delirium prevention is a current international hot topic, and delirium symptoms (fluctuating consciousness, agitation, hallucinations) align well with the No. 4 indication range

This direction's endpoint is a hard outcome with substantial clinical significance, but it requires daily postoperative assessment; we recommend limiting it to sites with an established elderly hip-fracture clinical pathway or ERAS team.

Population

Age 65+, MNA-SF ≤11 (malnutrition or nutritional risk) and MoCA <26. n=50–80

Primary endpoint

Dual endpoint of MoCA and MNA-SF

Secondary endpoints

AVLT auditory verbal learning, grip strength, weight and body composition, daily function (IADL), mood, feeding behavior

Design

Randomized control, 24 weeks

Publication angle

The "nutrition-cognition axis" is an interdisciplinary hot topic spanning geriatric medicine and clinical nutrition. Malnutrition is both a consequence and a risk factor of dementia, yet intervention research addressing this bidirectional relationship is very limited in Japan

Population

Post-stroke dysphagia (Grade 3+ on the Modified Water Swallow Test, or confirmed by VFSS/FEES), with limited oral intake or requiring tube feeding. n=40–60

Primary endpoint

Nutritional status (MNA-SF, weight, prealbumin) + FOIS Functional Oral Intake Scale

Secondary endpoints

Pneumonia incidence, NIHSS, MBI activities of daily living, time to tube removal, length of stay

Design

Randomized control, 12 weeks

Publication angle

Dysphagia is a leading cause of malnutrition and aspiration pneumonia after stroke, making collaboration between clinical nutrition and rehabilitation medicine a natural fit. Since the product can also be given via tube, patients with restricted oral intake can be covered throughout the study, avoiding attrition from a change in administration route

Population

Solid tumor patients, PG-SGA ≥4 (moderate-to-severe malnutrition) and BFI ≥4. n=40–60

Primary endpoint

PG-SGA score + BFI Brief Fatigue Inventory

Secondary endpoints

Weight and lean body mass, grip strength, chemotherapy completion rate and dose intensity, EORTC QLQ-C30, ECOG performance status

Design

Randomized control (standard nutrition support ± Chienomoto), 12 weeks

Publication angle

Malnutrition and cancer-related fatigue are the two main pillars of oncology supportive care, but they are usually studied separately. Combining both into a single endpoint framework enables a joint publication between clinical nutrition and oncology

This addresses the same clinical issue as O2 in oncology, led by a different department. To avoid duplicating the same topic within one institution, we recommend choosing one or the other.

Population

Ages 3–8 with clear picky/selective eating behavior, height or weight below the 10th percentile for age and sex, organic disease excluded. n=40–60

Primary endpoint

24-week change in weight and height Z-scores

Secondary endpoints

CEBQ Children's Eating Behaviour Questionnaire, daily energy and protein intake, blood zinc and ferritin, sleep, mood, parental feeding-related stress

Design

Randomized control (control arm receives feeding-behavior counseling), 24 weeks

Publication angle

Picky/selective eating is among the most common complaints in developmental and pediatric-nutrition clinics, parental anxiety runs very high, and follow-up adherence is very good. Both developmental clinics and clinical nutrition can lead this, and it is the fastest-enrolling direction in this domain

Population

Regular hemodialysis for 3+ months, FSS ≥4 or markedly reduced SF-36 vitality dimension. n=40–60

Primary endpoint

FSS Fatigue Severity Scale

Secondary endpoints

Post-dialysis recovery time, grip strength, nutrition markers (albumin, nPCR), KDQOL quality of life, depression and sleep

Safety endpoints (important)

Blood potassium, blood phosphate, changes in creatinine and BUN, dialysis adequacy (Kt/V) — must be monitored before and after every dialysis session

Design

Open-label pre/post control, 12 weeks

Publication angle

Dialysis-related fatigue occurs in over 60% of patients and is the symptom patients care about most yet receive the least intervention for. A joint effort between nephrology and clinical nutrition benefits from a fixed population and a naturally recurring follow-up rhythm (dialysis 3 times weekly), giving extremely low attrition

Required pre-check: In populations with renal impairment, electrolyte and metabolic load must be strictly monitored for any supplementary food product. This direction cannot be designed until testing data for the product's potassium, phosphorus, and sodium content is obtained first; if the documentation is insufficient, it should be put on hold.