A SMART Design to Improve Sleep Disturbance in Adolescents With Neurodevelopmental Disorders

Study Overview
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Brief Summary
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The objective of this K01 study was to pilot a sequential, multiple assignment, randomized trial (SMART) design to compare the impact of a sequence of sleep interventions, based on participant treatment response, to optimize sleep health in adolescents 10-18 years of age with neurodevelopmental disorders (NDDs).

Detailed Description
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The investigators conducted a sequential, multiple assignment, randomized trial (SMART) pilot feasibility study to inform implementation of a future full-scale SMART design that will be used to construct adaptive biobehavioral sleep intervention strategies involving melatonin, a behavioral sleep intervention (The Bedtime Bank), and their combination for the management of sleep disturbance in adolescents with neurodevelopmental (NDDs). Participants completed 1 week of baseline data collection, and than were randomly assigned to either melatonin or The Bedtime Bank. Response (>/= 18 minute average nightly increase in total sleep time [TST]) was measured at Week 4 and Week 8. Participants who responded (>/= 18 minute average nightly increase in TST) at Week 4 remained on the assigned intervention. Participants who were non-responsive at Week 4 were re-randomized to a different sleep intervention or combined interventions.

Official Title
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A SMART Design to Improve Sleep Disturbance in Adolescents With Neurodevelopmental Disorders

Conditions
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Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Sleep Disturbance

Intervention / Treatment
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* Dietary Supplement: Melatonin
* Behavioral: Bedtime Bank


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10-18 years and consistently living with parental (or legal guardian) supervision. Diagnostic report of confirmed NDD diagnosis (ASD or ADHD). Documentation of adolescent being classified as non-intellectually impaired (e.g. IQ>70). Parent report of adolescent spending less than or equal to 8 hours in bed per night on 3 or more nights per week in the past month or a composite score greater than 41 on the Children's Sleep Habits Questionnaire. Medication-free or on a stable dose of medications (no changes within 30 days prior to enrollment) with parental agreement to avoid changes in current medication (unless provider directed) during study participation. Exclusion Criteria: Unwillingness to stop melatonin 2 months prior to enrollment in the study. Parent report of adolescent with a known sleep disorder (e.g. sleep apnea). Adolescents who are not able to take oral medication. Adolescents who are visually impaired with known inability to detect light. Adolescents with an NDD with known genetic etiology (e.g. Angelman syndrome). Unwillingness to wear actigraph daily and complete daily sleep diary throughout the 9-week trial.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The investigators utilized a sequential, multiple assignment, randomized trial (SMART) pilot feasibility study design to inform implementation of a future full-scale SMART design that will be used to construct adaptive biobehavioral sleep intervention strategies involving melatonin, a behavioral sleep intervention (The Bedtime Bank), and their combination for the management of sleep disturbance in adolescents with neurodevelopmental (NDDs). Participants completed 1 week of baseline data collection, and than were randomly assigned to either melatonin or The Bedtime Bank. Response (>/= 18 minute average nightly increase in total sleep time [TST]) was measured at Week 4 and Week 8. Participants who responded (>/= 18 minute average nightly increase in TST) at Week 4 remained on the assigned intervention. Participants who were non-responsive at Week 4 were re-randomized to a different sleep intervention or combined interventions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin Only<br>In stage 1, participants in this arm will take 3 mg of melatonin 30 minutes before bedtime for 4 weeks. In stage 2, responders to melatonin will take 3 mg of melatonin 30 minutes before bedtime for an additional 4 weeks (repeat stage 1, for a total of 8 weeks). | Dietary Supplement: Melatonin<br>* Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime<br>|
| Experimental: The Bedtime Bank Only<br>In stage 1, participants in this arm will utilize The Bedtime Bank, a behavioral sleep intervention, for 4 weeks. In stage 2, responders to The Bedtime Bank will utilize The Bedtime Bank, a behavioral sleep intervention for an additional 4 weeks (repeat stage 1, for a total of 8 weeks). | Behavioral: Bedtime Bank<br>* The Bedtime Bank a novel behavioral sleep intervention, which is based upon contingency contracting and relies on a credit or debt-based system to hold adolescents accountable for maintaining a consistent bedtime and improve total sleep time.<br>|
| Experimental: Melatonin than Bedtime Bank<br>In stage 1, participants in this arm will take 3 mg of melatonin 30 minutes before bedtime for 4 weeks. In stage 2, non-responders to melatonin will utilize The Bedtime Bank, a behavioral sleep intervention, for 4 weeks. | Dietary Supplement: Melatonin<br>* Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime<br>Behavioral: Bedtime Bank<br>* The Bedtime Bank a novel behavioral sleep intervention, which is based upon contingency contracting and relies on a credit or debt-based system to hold adolescents accountable for maintaining a consistent bedtime and improve total sleep time.<br>|
| Experimental: Melatonin than Melatonin+Bedtime Bank Combo<br>In stage 1, participants in this arm will take 3 mg of melatonin 30 minutes before bedtime for 4 weeks. In stage 2, non-responders to melatonin will take 3 mg of melatonin 30 minutes before bedtime for an additional 4 weeks (repeat stage 1, for a total of 8 weeks) AND utilize The Bedtime Bank, a behavioral sleep intervention, for 4 weeks. | Dietary Supplement: Melatonin<br>* Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime<br>Behavioral: Bedtime Bank<br>* The Bedtime Bank a novel behavioral sleep intervention, which is based upon contingency contracting and relies on a credit or debt-based system to hold adolescents accountable for maintaining a consistent bedtime and improve total sleep time.<br>|
| Experimental: Bedtime Bank than Melatonin<br>In stage 1, participants in this arm will utilize The Bedtime Bank, a behavioral sleep intervention, for 4 weeks. In stage 2, non-responders to The Bedtime Bank will take 3 mg of melatonin 30 minutes before bedtime for 4 weeks. | Dietary Supplement: Melatonin<br>* Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime<br>Behavioral: Bedtime Bank<br>* The Bedtime Bank a novel behavioral sleep intervention, which is based upon contingency contracting and relies on a credit or debt-based system to hold adolescents accountable for maintaining a consistent bedtime and improve total sleep time.<br>|
| Experimental: Bedtime Bank than Bedtime Bank+Melatonin Combo<br>In stage 1, participants in this arm will utilize The Bedtime Bank, a behavioral sleep intervention, for 4 weeks. In stage 2, non-responders to The Bedtime Bank will utilize The Bedtime Bank, a behavioral sleep intervention for an additional 4 weeks (repeat stage 1, for a total of 8 weeks) AND take 3 mg of melatonin 30 minutes before bedtime for 4 weeks. | Dietary Supplement: Melatonin<br>* Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime<br>Behavioral: Bedtime Bank<br>* The Bedtime Bank a novel behavioral sleep intervention, which is based upon contingency contracting and relies on a credit or debt-based system to hold adolescents accountable for maintaining a consistent bedtime and improve total sleep time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actigraphy (Total Sleep Time) | Objective measure of sleep patterns based on the correlation between sleep-wake state and motor activity. A sleep diary was utilized to guide data analysis. | To be worn daily for the entirety of the study (9 weeks total). Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Baseline, Week 4, and Week 8) | 
| AARP- Abbreviated Acceptability Rating Profile | Parents completed the Abbreviated Acceptability Rating Profile (AARP), which will be used to indicate minimal treatment acceptability. Parent(s) and adolescent completed a semi-structured interview to discuss treatment acceptability. Min/Max Values: 8-48 Higher scores=more acceptable/better | Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Week 4 and Week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Melatonin | The Genway Biotech Melatonin ELISA Kit (San Diego, CA) will allow for the analysis and quantification of endogenous melatonin. | Completed once during the baseline week prior to first stage randomization. Results reported by first stage randomization group. | 
| PROMIS Pediatric Item Bank Sleep Related Impairment | An 8-item questionnaire used to measure self-reported alertness, sleepiness, tiredness, and functional impairments associated with sleep problems during waking hours. PROMIS measures generate T-scores. T-scores are standard scores with a mean of 50 and standard deviation of 10 in a reference population (usually U.S. general population). Higher scores=worse sleep related impairment | Baseline, Week 4, & Week 8-PROMIS Pediatric Item Bank Sleep Related Impairment t-score. | 
| PROMIS Pediatric Item Bank Sleep Disturbance | An 8-item questionnaire used to measure self-reported perceptions of sleep quality, depth, and restoration. This includes perceived difficulties getting to sleep and staying asleep, as well as sleep satisfaction. PROMIS measures generate T-scores. T-scores are standard scores with a mean of 50 and standard deviation of 10 in a reference population (usually U.S. general population). Higher scores=worse sleep disturbance | Baseline, Week 4, & Week 8 PROMIS Pediatric Item Bank Sleep Disturbance t-scores/SE. | 
| Cleveland Adolescent Sleepiness Questionnaire (CASQ) | A sixteen-item instrument used to measure daytime sleepiness in adolescents 11-17 years of age. Score ranges between 16-80. Higher scores would indicate greater sleepiness | Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Baseline, Week 4, and Week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Sleep Disturbance, Melatonin, ASD, ADHD