MELATONIN for Major depressive episode | Insomnia

Inclusion criteria

• {"criterion_text":"- 1-Aged 18 to 65 years."}
• {"criterion_text":"- 2- Diagnosed with Major Depressive Episode (MDE) in the context of a unipolar disorder (DSM-5 criteria) and a MADRS score ≥20 (threshold validated for moderate MDE)."}
• {"criterion_text":"- 3- Comorbid insomnia (DSM-5 criteria) with an ISI score ≥8 (threshold validated for mild and clinically significant insomnia)."}
• {"criterion_text":"- 4- Not exposed to antidepressants of any class in the month prior to inclusion"}
• {"criterion_text":"- 5- Not exposed to light therapy in the month prior to inclusion."}
• {"criterion_text":"- 6- Patients receiving outpatient or inpatient care for a treatment duration of 8 weeks"}
• {"criterion_text":"- 7- Ability to understand and sign the informed consent."}

Exclusion criteria

• {"criterion_text":"- 1- Subjects under guardianship or deprived of liberty."}
• {"criterion_text":"- 10- Participation in another interventional study during the course of the trial"}
• {"criterion_text":"- 11- Known hypersensitivity to melatonin."}
• {"criterion_text":"- 12- Contraindication to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs)."}
• {"criterion_text":"- 2- Ophthalmic diseases (cataracts, glaucoma, age-related macular degeneration, etc.) or diseases affecting the retina (retinitis pigmentosa, diabetes, herpes, etc.)."}
• {"criterion_text":"- 3- The following disorders (according to DSM-5): Schizophrenia and other psychotic disorders; Bipolar disorder, particularly (hypo)manic episodes (YMRS score ≥ 12); Other unstable mental disorders, such as substance use disorders, including alcohol and tobacco"}
• {"criterion_text":"- 4- Other unstable general medical conditions."}
• {"criterion_text":"- 5- Pregnant or breastfeeding women."}
• {"criterion_text":"- 6- Hypersomnia with prolonged total sleep time secondary to MDE according to ICSD-3 criteria."}
• {"criterion_text":"- 7- Therapeutic resistance of the current MDE (2 antidepressants from different classes)."}
• {"criterion_text":"- 8- Presence of a high suicide risk, assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS, score ≥ 4)."}
• {"criterion_text":"- 9- Treatment with melatonin at the time of inclusion."}

Primary endpoints

• {"endpoint_text":"- Montgomery-Åsberg Depression Rating Scale (MADRS) score at 8 weeks (Week 8, Visit 3 – clinical evaluation visit) adjusted for the baseline score (Week 0, Visit 0 – inclusion and randomization visit) in each of the four treatment arms","definition_or_measurement_approach":"MADRS clinical assessment at Week 8 (Visit 3) with adjustment for baseline MADRS measured at Week 0 (Visit 0, inclusion/randomisation). Endpoint measured separately in each of the four treatment arms."}

Secondary endpoints

• {"endpoint_text":"- 1.\tMADRS score at 1, 4, 8 weeks, and 3 months: o\tTherapeutic response (50% reduction in MADRS score). o\tRemission (MADRS score ≤ 10).","definition_or_measurement_approach":"MADRS measured at Weeks 1, 4, 8 and at 3 months. Therapeutic response defined as ≥50% reduction in MADRS; remission defined as MADRS ≤10."}
• {"endpoint_text":"- 2.\tSubjective sleep quality at 1, 4, 8 weeks, and 3 months: sleep and sleep-wake rhythm self-questionnaires","definition_or_measurement_approach":"Self-reported sleep and sleep-wake rhythm questionnaires administered at Weeks 1, 4, 8 and at 3 months."}
• {"endpoint_text":"- 3.\tObjective actigraphy parameters at 1, 4, and 8 weeks: o\tSleep parameters: total sleep time, nocturnal awakenings (WASO), fragmentation index, sleep efficiency (total sleep time/total time in bed), time spent in bed. o\tRhythm parameters: relative amplitude, stability, and variability of sleep-wake rhythms, L5 and M10 phase markers (onset of the least active 5 hours and most active 10 hours).","definition_or_measurement_approach":"Actigraphy-derived objective sleep parameters and rhythm metrics assessed at Weeks 1, 4 and 8 (total sleep time, WASO, fragmentation index, sleep efficiency, time in bed; rhythm measures including relative amplitude, stability/variability, L5 and M10 onset)."}
• {"endpoint_text":"- 4.\tSubjective sleep diary parameters at 1, 4, and 8 weeks.","definition_or_measurement_approach":"Participant-completed sleep diary entries assessed at Weeks 1, 4 and 8."}
• {"endpoint_text":"- 5.\tSlope of longitudinal evolution of the MADRS score","definition_or_measurement_approach":"Analysis of longitudinal trajectory (slope) of MADRS scores over time from baseline through follow-up visits."}
• {"endpoint_text":"- 6.\tTime (in days) to therapeutic response (maximum assessment at 3 months).","definition_or_measurement_approach":"Time-to-event measured in days from baseline to therapeutic response (as defined above), with maximum follow-up to 3 months."}
• {"endpoint_text":"- 7.\tSide effects questionnaire (PRISE-M) at 1, 4, and 8 weeks","definition_or_measurement_approach":"PRISE-M adverse effects questionnaire administered at Weeks 1, 4 and 8 to assess side effects."}
• {"endpoint_text":"- 8.\tMood state and overall functioning questionnaires (YMRS, C-SSRS, QIDS-SR, GAG7, CGI) at 1, 4, 8 weeks, and 3 months","definition_or_measurement_approach":"Standardised mood and functioning questionnaires (YMRS, C-SSRS, QIDS-SR, GAD7, CGI) administered at Weeks 1, 4, 8 and at 3 months."}

France

Earliest CTIS Part Ii Submission Date

08-04-2025

Latest Decision Or Authorization Date

12-05-2025

Processing Time Days

34

Number Of Sites

5

Number Of Participants

184

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France