Melatonin Effects on Sleep and Circadian Rhythm in Youth and Young Adults With At-risk Symptoms

Not Applicable

Completed

• Conditions: Psychosis; Sleep
• Interventions: Other: Placebo; Drug: oral melatonin tablets (NatureMade brand)

• Registration Number: NCT03826563
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

Randomized control trial assessing supplemental melatonin for youth with at-risk or psychotic symptoms.

Detailed Description

Context: Sleep disturbances and circadian dysrhythmias have been associated with psychotic symptom severity in Psychosis Spectrum (PS) youths. Supplemental melatonin is a safe over-the-counter dietary supplement, and several studies have found that melatonin improves sleep across several childhood neuropsychiatric disorders.

Objectives: Investigators seeks to determine whether supplemental melatonin improves sleep and circadian alignment in PS youth. Investigators will also investigate whether supplemental melatonin affects psychotic symptoms, neurocognition, and peripheral inflammatory and oxidative stress markers.

Study Design: Parallel group, double-blind, randomized, placebo-controlled trial Setting/Participants: 40 PS youths ages 11-30 years old (throughout the protocol we use "youth" to describe this age group) with sleep disturbances will be recruited from an extant cohort of PS youths followed by our lab in the Philadelphia Neurodevelopmental Cohort (PNC), Children's Hospital of Philadelphia (CHOP), University of Pennsylvania (UPenn), and the surrounding community. The study will be conducted at CHOP and UPenn.

Study Interventions and Measures: Youths will be randomized to receive pill placebo or oral melatonin. Participants will take melatonin (or placebo) at the same time every evening for 2 weeks (final dose range 2.5-10 mg nightly). Outcomes will be assessed at 1 week, 2 weeks, and 6-months. Primary outcomes will be changes in self-reported sleep and actigraph-measured sleep and circadian rhythm. Secondary outcomes will be psychotic symptoms, neurocognition, and peripheral blood markers of inflammation and oxidative stress.

Study Timeline

• Study First Submitted: 2019-01-17
• Study Start: 2019-01-18
• Study First Submitted QC: 2019-01-30
• Study First Posted: 2019-02-01
• Primary Completion: 2023-04-07
• Study Completion: 2023-04-07
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-05
• Last Update Posted: 2023-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Males or females age 11-30 years old and patient at the Children's Hospital of Philadelphia (CHOP), University of Pennsylvania (UPenn), or member of the surrounding community
• Subthreshold psychosis-risk positive symptoms (e.g. hallucinations or unusual beliefs) on the Structured Interview of Psychosis-Risk Syndromes (SIPS)
• At least mild sleep disturbances on the SIPS (>=1 on the SIPS sleep item (G1)) with difficulties with
• Must have difficulties with sleep onset, sleep awakenings, or maintaining a regular sleep schedule.
• Willingness to report all changes in medications and therapy during the study
• Intelligence Quotient (IQ) > 70
• If female, not breastfeeding and not pregnant and willing to use effective birth control for the duration of the study (e.g. abstinence or oral contraception).
• Medically healthy
• Fluent in English

Exclusion Criteria

• Psychiatric symptoms with imminent safety concern (e.g. intractable and escalating suicidal ideation)
• Currently taking melatonin, having taken melatonin daily within the 2 weeks prior to Visit 1, or having a history of an intolerance or allergy to melatonin.
• Medication or treatment changes in the 4 weeks prior to Visit 1 .
• Anticipated medication or other treatment (e.g. type of psychotherapy) changes in the three weeks after study enrollment.
• IQ <70
• Taking any medication whose potential interactions with melatonin present a significant risk or limit the effect of melatonin in the judgment of the investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will receive pill placebo nightly
Melatonin	oral melatonin tablets (NatureMade brand)	Subjects will receive oral melatonin tablets 2.5-10mg nightly for 2 weeks. All will receive melatonin 5mg for one week, then at the 1 week visit, the dose can be continued at 5mg or adjusted to 2.5mg or 10mg nightly based on clinical assessment of patient response and side effects.

Primary Outcome Measures

Name	Time	Method
Actigraph-measured sleep (increased total sleep time)	Change in total sleep time from melatonin randomization day (Day 0) to Day 14	Actigraph-measured total sleep time will be used to assess actigraph-measured sleep efficacy, Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software.

Secondary Outcome Measures

Name	Time	Method
Improved self-reported sleep	Change in total PSQI from melatonin randomization day (Day 0) to Day 14	Pittsburgh Sleep Quality Index (PSQI); range is 0-21, with higher scores indicating poorer sleep

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States