Chronobiological Intervention with Melatonin and Light Therapy in Idiopathic Hypersomnia: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this clinical trial is to evaluate the **efficacy** of a 6-week chronobiological treatment regimen in adult patients diagnosed with **idiopathic hypersomnia**. This regimen combines evening administration of fast-release 2 mg **melatonin** with morning bright light therapy. The trial aims to demonstrate a reduction in idiopathic hypersomnia symptoms, as measured by the Idiopathic Hypersomnia Severity Scale (IHSS), compared to a placebo treatment consisting of an evening placebo drug and morning placebo light. The clinical relevance of this study lies in its potential to offer an effective therapeutic strategy for managing symptoms of idiopathic hypersomnia, a condition characterized by excessive daytime sleepiness and prolonged nighttime sleep, which significantly impacts patients' quality of life.

The clinical trial focuses on adult patients diagnosed with **idiopathic hypersomnia**. The study population includes both male and female participants, aged between 18 and 45 years, who have been diagnosed according to the ICSD-3 criteria. Participants must have experienced symptoms for more than three months and have a total sleep time of at least 11 hours, as confirmed by a 24-hour continuous polysomnography conducted within the last five years. The trial does not involve a vulnerable population. Participants are required to maintain stable medication throughout the 11-week study period and must be able to comply with the chronobiotherapy schedule. Female participants are required to use effective contraception or practice sexual abstinence during the month preceding inclusion and throughout the study. The sponsor has not provided information regarding the total number of participants. Participants must have given written informed consent and be affiliated with social security insurance. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of a **chronobiological treatment** in adult patients diagnosed with **idiopathic hypersomnia**. This study is a prospective, double-blind, randomized, placebo-controlled trial. The primary objective is to assess the impact of a 6-week treatment regimen combining evening administration of 2 mg of fast-release **melatonin** and morning bright light therapy, compared to a placebo regimen, on reducing symptoms as measured by the Idiopathic Hypersomnia Severity Scale (IHSS). The trial is expected to conclude by October 30, 2026, with recruitment starting on November 1, 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-45 years), diagnosis of idiopathic hypersomnia according to ICSD-3 criteria, and stable medication use. Following the screening, participants will be randomized to receive either the active treatment or placebo for a duration of 6 weeks. Follow-up visits will be scheduled to monitor compliance, assess any adverse events, and evaluate treatment efficacy. The end-of-study visit will involve a final assessment of the IHSS score to determine the primary endpoint, which is the difference in IHSS score before and after the treatment period.

The expected length of participant involvement is approximately 11 weeks, including the screening, treatment, and follow-up phases. Conditions that may lead to early termination from the study include non-compliance with the treatment regimen, withdrawal of consent, or the occurrence of significant adverse events. Participants are required to maintain stable medication use and adhere to the study schedule to ensure the integrity of the trial results.

The clinical trial involves the administration of **Mélatonine à libération immédiate**, an experimental medication formulated as a capsule. The active substance in this medication is **melatonin**, a chemical compound. The dosage is set at 2 mg per capsule, with a maximum daily dose of 2 mg. The total maximum dose over the treatment period is 90 mg, administered over a maximum treatment period of 45 days. The route of administration is oral, and the medication is intended for evening use as part of a chronobiological treatment regimen. The primary objective is to assess the efficacy of this treatment in reducing symptoms of idiopathic hypersomnia.

In addition to the experimental treatment, a placebo is utilized in the study. The placebo is designed to mimic the experimental medication in appearance and administration but contains **cellulose microcristalline** as the inactive substance. The placebo is administered orally in the same capsule form as the experimental treatment, ensuring blinding in the double-blind, randomized, placebo-controlled trial. The placebo is administered in the evening, in conjunction with a placebo light therapy in the morning, to serve as a comparator to the active treatment regimen.

The efficacy of the clinical trial will be assessed by evaluating the impact of the treatment on **Idiopathic Hypersomnia** (IH) symptoms. The primary endpoint for efficacy is the change in the Idiopathic Hypersomnia Severity Scale (IHSS) score, which will be measured before and after a 6-week treatment period. Participants will receive either active chronobiotherapy, consisting of 2 mg of fast-release melatonin in the evening and bright light therapy (BLT) in the morning, or a placebo treatment, which includes a placebo drug and placebo light. The IHSS is a validated scale used to quantify the severity of IH symptoms, providing a reliable measure for assessing treatment efficacy.