Evening melatonin plus morning bright light for idiopathic hypersomnia

a Chronobiological Treatment Combining Evening Melatonin and Morning Light Therapy in Idiopathic Hypersomnia: a Prospective, Double Bind, Randomized, Placebo-controlled -Trial

This trial will test whether taking melatonin at night and using bright light in the morning reduces daytime sleepiness and long sleep times in adults with idiopathic hypersomnia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years to 40 Years
• Sex: All
• Sponsor: University Hospital, Strasbourg, France (other)
• Locations: 1 site (Strasbourg)
• Trial ID: NCT06252571 on ClinicalTrials.gov

What this trial studies

This is a prospective, double-blind, randomized, placebo-controlled phase 2 trial testing a chronobiological combination of evening melatonin and morning bright light versus placebo pill and placebo light. Adults aged 18–40 with idiopathic hypersomnia confirmed by ICSD-3 criteria and a 24-hour polysomnography showing ≥11 hours total sleep time are eligible. Participants remain on stable medications, follow the assigned nightly and morning interventions, and are followed across a roughly 10-week participation window. Outcomes will focus on daytime sleepiness, sleep duration, and symptoms such as sleep inertia using standardized measures.

Who should consider this trial

Good fit: Adults 18–40 with a confirmed diagnosis of idiopathic hypersomnia (ICSD-3) and objective ≥11-hour total sleep time on a recent 24-hour polysomnography who can follow the timing of melatonin and light therapy are ideal candidates.

Not a fit: People outside the 18–40 age range, those without objective long sleep times on 24-hour polysomnography, or patients unable to comply with the timing schedule or requiring disallowed medications may not benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could offer a low-risk, non-controlled-substance treatment to reduce excessive sleepiness and improve daily functioning in people with idiopathic hypersomnia.

How similar studies have performed: The evening melatonin plus morning bright light combination is a validated chronotherapy for delayed sleep-wake phase disorder and melatonin is used empirically in idiopathic hypersomnia, but randomized placebo-controlled data specifically in idiopathic hypersomnia are limited.

Eligibility criteria

Inclusion criteria:

* Male or female patient
* Age ≥ 18 and ≤ 40 years at signature of informed consent form
* Diagnosed with Idiopathic hypersomnia in a reference/competence center of hypersomnia rare disease network according to ICSD-3 criteria (International classification of sleep disorders) with symptoms lasting since \>3 months and a total sleep time ≥11hours objectified with a 24h continuous polysomnography realized during the last 12 months
* Patient with stable medication in the month preceding inclusion and throughout the 10 weeks of participation to the study (except for drugs excluding participation. See list below).
* Patient able to be compliant with therapy during the required time and at the set schedule.
* For female patient: effective efficient contraception during the month preceding the inclusion and all along the study
* Patient who have given written informed consent and are able to understand the objectives and risks associated to the research.
* Patient affiliated to a social security insurance

Exclusion criteria:

1. Criteria related to the underlying disorder (other forms of hypersomnia or sleep disorder)

   * Other primary or secondary hypersomnia (narcolepsy, Kleine-Levin syndrome, post-traumatic hypersomnia, hypersomnia due to medication or substance abuse…)
   * Other intrinsic sleep disorder according to ICSD-3 criteria (sleep apnea syndrome, restless legs syndrome, insomnia)
2. Criteria related to pathologies associated with particular risks or consumption of substances that may affect sleep or alertness:

   * Significant psychiatric comorbidities (current severe depressive episode based on the DSM-V criteria, risk of suicide, schizophrenia, bipolar disorder).
   * Known systemic or severe acute disease (auto-immune diseases…)
   * Substance / alcohol /cigarette dependence
   * Consumption of excessive amounts of caffeine, defined as greater than 600 mg of caffeine of coffee, tea, cola, energy drinks, or other caffeinated beverages per day (1 cup of coffee is approximately 120 mg)
3. Criteria related to circadian rhythms disturbances

   * Recent transmeridian travel (\> 2 time zones) within the month before the start of the study
   * History of shift/night work reported within the 6 months preceding the study
   * Irregular sleep habits (more than 2 hours of delay or advance in bedtime ≥ 3 nights over a week)
   * Circadian sleep-wake rhythm disorders according to ICSD-3 criteria (advanced or delayed sleep phase syndrome, …)
4. criteria related to medications (within 1 month prior to study)

   * Sleep promoting drugs (benzodiazepines, z-drugs, sodium oxybate, antihistaminics…)
   * Wake promoting-drugs (modafinil, pitolisant, methylphenidate, solriamfétol chlorhydrate)
   * Psychotropics and drugs inducing level 3 sleepiness according to the ANSM (French National Agency for Medicines and Health Products Safety) gradation.
   * beta-blockers
   * regular anti-inflammatory drug intake
   * Exogenous melatonin and/or serotonin and or tryptohane (as a drug or a dietary supplement)
5. Criteria related to relative contra-indications to light therapy

   * Medical history of ophthalmologic diseases causing visual impairment: retinopathy, age-related macular degeneration, macular hole, epiretinal membrane; cataract; optic neuropathy.
   * On-going medication with a photosensibilizing drug
   * Photosensitive epilepsia or migraine
6. Criteria relative to exogenous melatonin administration

   * Prior intolerance to cellulose or exogenous melatonin
   * Drugs metabolized by CYP1A2 intake within 1 month prior to study: antivitamin K, fluvoxamine, cimetidine, carbamazepine, rifampicin…
7. Criteria relative to relative contraindications of e-celsius capsules

   * Patient weighting less than 40 kg
   * Medical history of motility disorders of the gastrointestinal tract and intestinal disorders that can lead to obstruction of the digestive tract, including diverticula, Crohn disease, surgical procedures in the gastrointestinal tract
   * Known swallowing disorders
   * In presence of a pacemaker or electro-medical implant.
   * Patient who has to undergo strong electromagnetic field during the period of use of the system (MRI)
8. Criteria relative to regulation:

   * Pregnancy, breastfeeding.
   * Participation in another interventional clinical trial with an exclusion period
   * Patient with difficulty to read or understand French, or inability to understand the delivered information
   * Patient in emergency situation
   * Patient in life-threatening situation
   * Patient under justice safeguard
   * Patient under guardianship or limited guardianship
   * Patient unwilling to refrain from driving and/or operating dangerous or hazardous machinery during times of heightened sleepiness or fatigue due to the medication

Where this trial is running

Strasbourg

• Hôpitaux Universitaires de Strasbourg — Strasbourg, France (RECRUITING)

Study contacts

• Study coordinator: Patrice BOURGIN, MD

Conditions: Idiopathic Hypersomnia, hypersomnia, light, melatonin, sleep, chronobiotherapy