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

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).

Study Overview

• Status: Completed
• Conditions: Sleep Disturbance; Autism Spectrum Disorder; Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Dietary supplement: Melatonin; Behavioral: Bedtime Bank

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5330
      • University of Nebraska Medical Center, Center for Nursing Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin Only; 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; Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime
Experimental: The Bedtime Bank Only; 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; 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.
Experimental: Melatonin than Bedtime Bank; 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; Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime; Behavioral: Bedtime Bank; 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.
Experimental: Melatonin than Melatonin+Bedtime Bank Combo; 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; Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime; Behavioral: Bedtime Bank; 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.
Experimental: Bedtime Bank than Melatonin; 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; Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime; Behavioral: Bedtime Bank; 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.
Experimental: Bedtime Bank than Bedtime Bank+Melatonin Combo; 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; Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime; Behavioral: Bedtime Bank; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: National Institute of Nursing Research (NINR)
• Investigators: Principal Investigator: Alyson E Hanish, PhD, MSN, RN, University of Nebraska

Publications and helpful links

General Publications

• Almirall D, Compton SN, Gunlicks-Stoessel M, Duan N, Murphy SA. Designing a pilot sequential multiple assignment randomized trial for developing an adaptive treatment strategy. Stat Med. 2012 Jul 30;31(17):1887-902. doi: 10.1002/sim.4512. Epub 2012 Mar 22.
• Gruber R, Somerville G, Bergmame L, Fontil L, Paquin S. School-based sleep education program improves sleep and academic performance of school-age children. Sleep Med. 2016 May;21:93-100. doi: 10.1016/j.sleep.2016.01.012. Epub 2016 Feb 15.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: November 2, 2018
• First Posted (Actual): November 5, 2018

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Melatonin; ADHD; Attention Deficit Hyperactivity Disorder; ASD; Autism Spectrum Disorder; Sleep Disturbance
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Child Development Disorders, Pervasive; Dyssomnias; Parasomnias; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Hyperkinesis; Neurodevelopmental Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 0775-18-FB; 1K01NR017465-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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