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

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 ofhypersomnia rare disease network according to ICSD-3 criteria (Internationalclassification of sleep disorders) with symptoms lasting since >3 months and a totalsleep time ≥11hours objectified with a 24h continuous polysomnography realizedduring 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 setschedule.

• For female patient: effective efficient contraception during the month preceding theinclusion and all along the study

• Patient who have given written informed consent and are able to understand theobjectives 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 sleepdisorder)

• Other primary or secondary hypersomnia (narcolepsy, Kleine-Levin syndrome,post-traumatic hypersomnia, hypersomnia due to medication or substanceabuse...)

• Other intrinsic sleep disorder according to ICSD-3 criteria (sleep apneasyndrome, restless legs syndrome, insomnia)

2. Criteria related to pathologies associated with particular risks or consumption ofsubstances that may affect sleep or alertness:

• Significant psychiatric comorbidities (current severe depressive episode basedon 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 ofcaffeine of coffee, tea, cola, energy drinks, or other caffeinated beveragesper 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 startof 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 ≥ 3nights over a week)

• Circadian sleep-wake rhythm disorders according to ICSD-3 criteria (advanced ordelayed 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, solriamfétolchlorhydrate)

• 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 dietarysupplement)

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, epiretinalmembrane; 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: antivitaminK, 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 andintestinal disorders that can lead to obstruction of the digestive tract,including diverticula, Crohn disease, surgical procedures in thegastrointestinal tract

• Known swallowing disorders

• In presence of a pacemaker or electro-medical implant.

• Patient who has to undergo strong electromagnetic field during the period ofuse 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 tounderstand 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 orhazardous machinery during times of heightened sleepiness or fatigue due to themedication