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

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

Detailed Description
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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.

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

Conditions
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Sleep, Psychosis

Intervention / Treatment
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* Drug: oral melatonin tablets (NatureMade brand)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will receive pill placebo nightly | Other: Placebo<br>* pill placebo<br>|
| Experimental: Melatonin<br>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. | Drug: oral melatonin tablets (NatureMade brand)<br>* melatonin tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actigraph-measured sleep (increased total sleep time) | 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. | Change in total sleep time from melatonin randomization day (Day 0) to Day 14 | 

Secondary Outcome Measures

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