Sleep Disturbances in Children and Adolescents With Post-traumatic Stress Disorder (PTSD): a Randomized Double-blind Placebo-controlled Trial to Investigate the Efficacy of Pediatric Prolonged-release Melatonin (MelatoSomKids)

Among the most sensitive and persistent symptoms of post-traumatic stress disorder (PTSD) in children are sleep disturbances in the insomnia spectrum (sleep onset disturbances, fragmented sleep with multiple nocturnal awakening, early morning awakening) as well as nightmares, affecting over 50% of children and adolescents one year after the initial trauma. There are currently no gold standard treatments or pharmacological treatment recommendations specifically for these sleep disturbances in children and adolescents with PTSD, despite the fact that they have a significant effect on daytime functioning and overall mental health of the children and their families. If not treated appropriately, these sleep disturbances in children and adolescents persist over time, and further increase anxiety in children. Sleep disturbances associated with PTSD are predictive of the persistence and long-term outcome of PTSD itself and associated depressive symptomatology, and of a decreased response rate to cognitive-behavioral psychotherapy for PTSD.

We have previously shown in an international multicenter study that pediatric prolonged release melatonin (PedPRM) has high beneficial effects on sleep disturbances of the insomnia spectrum in children ages 2-17.5 years with autism spectrum disorder, and consecutive positive effects on children's daytime behavior, including anxiety and depressive symptomatology. Its benefit-risk ratio has proven to be excellent over a 2-year follow-up. Beyond its therapeutic benefit on mental health through improvement of sleep, melatonin may have a direct effect on reducing anxiety levels and overall daytime functioning in children, as well as sleep and daytime function in caregivers.

Our study will be the first randomized controlled trial investigating the efficacy of prolonged release melatonin on sleep disturbances in children and adolescents with PTSD, as well as on PTSD symptoms, associated daytime function and overall mental health in these children and their caregivers.

Study Overview

• Status: Not yet recruiting
• Conditions: Post-traumatic Stress Disorder (PTSD); Current Significant Sleep Disturbances
• Intervention / Treatment: Drug: pediatric, prolonged released melatonin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Julie ROLLING, MD; Phone Number: 0033 03 88 11 54 82; Email: julie.rolling@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France, 67091
    • Hôpitaux Universitaires de Strasbourg
    • Contact: Julie ROLLING, MD; Phone Number: 0033 03 88 11 54 82; Email: julie.rolling@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Children and adolescents (2 -17.5 years) with:

• A diagnosis of post-traumatic stress disorder (PTSD) as defined by DSM-5 (American Psychiatric Association, 2013)
• Current significant sleep disturbances defined as ≤6 hours of continuous sleep and/or ≥0.5-hour sleep latency from lights-off on 3 out of 5 nights and/or nightmare disorder as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3, Sateia, 2014), for a minimum 3 months, based on parent report and patient medical history
• No response to at least 4 weeks of sleep hygiene
• Negative pregnancy test for females with childbearing potential
• Written informed consent provided by both parents or a legal guardian, as well as the children / adolescents themselves, if possible
• Stable doses of non-excluded medications for at least 3 months

Exclusion Criteria:

• Known systemic or severe acute disease whose care would hinder attendance at appointments
• Pregnancy, breastfeeding
• Known diagnosis of another significant sleep disorder (e.g., moderate to severe sleep apnea)
• Treatment with any form of melatonin within 2 weeks prior to screening
• Unresponsiveness to previous prolonged release melatonin within the 2 years prior to the study
• Known allergy to melatonin or lactose
• Use of prohibited medication (benzodiazepine, z-drug, antihistaminic, among others) within 2 weeks prior to screening
• Start of a cognitive behavioural therapy (CBT) targeting sleep disturbances or mood disorders, within 6 weeks before study inclusion
• Participation in a clinical trial within the last month prior to the study
• Transmeridian travel (> 2 time zones) within the month before the start of the study
• Females not using contraceptives who are sexually active, pregnant, and/or breastfeeding
• Other reasons: inability to receive clear information, inability to participate in the entire study, lack of coverage by the social security system, refusal to sign consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active therapy; melatonin	Drug: pediatric, prolonged released melatonin; Initial dosage will be of 2mg, and eventually increased to 5mg at dose optimization visit if no or insufficient improvement has been observed in the first 3 weeks of treatment
Placebo Comparator: Placebo therapy; placebo	Drug: Placebo; Initial dosage will be of 2 tablets, and eventually increased to 5 tablets at dose optimization visit if no or insufficient improvement has been observed in the first 3 weeks of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in sleep-diary derived total sleep time after 13 weeks of treatment	At Day 0 and day 92

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 7679

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No