Psychosis, Sleep
Conditions
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.
Interventions
DRUGoral melatonin tablets (NatureMade brand)
melatonin tablets
OTHERPlacebo
pill placebo
Sponsors
University of Pennsylvania
Brain and Behavior Research Foundation (NARSAD Young Investigator Award, Grant Number 26742)
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Only the pharmacy will know the randomization arms.
Eligibility
Sex/Gender
ALL
Age
11 Years to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Decreased actigraph-measured sleep latency | Change in actigraph-measured sleep onset latency from melatonin randomization day (Day 0) to Day 14 | How long it takes a participant to fall asleep; Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Sleep latency is an Actilife software outcome. |
| Increased actigraph-measured sleep efficiency | Change from Randomization day (Day 0) to Day 14. | Amount of time participant spends sleeping divided by the amount of time the patient spends in bed. Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Sleep efficiency is an Actilife software outcome. |
| Lower autocorrelation function | Change in actigraph-measured autocorrelation from melatonin randomization day (Day 0) to Day 14 | Ac is the slope of the time correlation line (log-trans- formed); indicative of rhythm fragmentation; lower values represent less fragmented rhythms. Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Autocorrelation function is an Actilife software outcome. |
| Increased activity (M10) | Change in actigraph-measured M10 from melatonin randomization day (Day 0) to Day 14 | mean activity level during the most active 10 h of the day; higher values are indicative of a more active lifestyle. M10 is an Actilife software output. |
Countries
United States
Outcome results
None listed