Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, Sleep Disturbance
Conditions
Keywords
Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Sleep Disturbance, Melatonin, ASD, ADHD
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTMelatonin
Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime
BEHAVIORALBedtime 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.
Sponsors
National Institute of Nursing Research (NINR)
University of Nebraska
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Actigraphy (Total Sleep Time) | 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) | 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. |
| AARP- Abbreviated Acceptability Rating Profile | Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Week 4 and Week 8) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Melatonin | Completed once during the baseline week prior to first stage randomization. Results reported by first stage randomization group. | The Genway Biotech Melatonin ELISA Kit (San Diego, CA) will allow for the analysis and quantification of endogenous melatonin. |
| PROMIS Pediatric Item Bank Sleep Related Impairment | Baseline, Week 4, & Week 8-PROMIS Pediatric Item Bank Sleep Related Impairment t-score. | 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 |
| PROMIS Pediatric Item Bank Sleep Disturbance | Baseline, Week 4, & Week 8 PROMIS Pediatric Item Bank Sleep Disturbance t-scores/SE. | 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 |
| Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Baseline, Week 4, and Week 8) | 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 |
Countries
United States
Participant flow
Recruitment details
See uploaded study protocol that includes recruitment details.
Participants by arm
| Arm | Count |
|---|---|
| First Stage Melatonin Stage 1: Participants in this arm will take 3 mg of melatonin 30 minutes before bedtime.
Melatonin: Melatonin (liquid, immediate release, 3 mg) 30 minutes before bedtime | 20 |
| First Stage Bedtime Bank Stage 1: Participants in this arm will utilize the Bedtime Bank, a behavioral sleep intervention.
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. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Stage Treatment | Protocol Violation | 3 | 3 | 0 | 0 | 0 | 0 |
| First Stage Treatment | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | First Stage Melatonin | First Stage Bedtime Bank | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 20 Participants | 40 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.45 years STANDARD_DEVIATION 2.95 | 13.00 years STANDARD_DEVIATION 2.05 | 13.23 years STANDARD_DEVIATION 2.52 |
| Diagnosis ADHD only | 17 Participants | 14 Participants | 31 Participants |
| Diagnosis Autism (with or without ADHD) | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 17 Participants | 33 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 3 / 27 | 2 / 26 | 0 / 13 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 | 0 / 13 |
Outcome results
Primary
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
Time frame: Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Week 4 and Week 8)
Population: Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Week 4 and Week 8). Data was analyzed based on first stage randomization regardless of whether participants were responders or non-responders.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| First Stage Melatonin | AARP- Abbreviated Acceptability Rating Profile | Week 4 | 38.84 units on a scale | Standard Deviation 7.19 |
| First Stage Melatonin | AARP- Abbreviated Acceptability Rating Profile | Week 8 | 38.84 units on a scale | Standard Deviation 6.83 |
| First Stage Bedtime Bank | AARP- Abbreviated Acceptability Rating Profile | Week 4 | 34.00 units on a scale | Standard Deviation 6.36 |
| First Stage Bedtime Bank | AARP- Abbreviated Acceptability Rating Profile | Week 8 | 37.89 units on a scale | Standard Deviation 5.49 |
Primary
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.
Time frame: 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)
Population: Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Baseline, Week 4, and Week 8). Data was analyzed based on first stage randomization regardless of whether participants were responders or non-responders.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| First Stage Melatonin | Actigraphy (Total Sleep Time) | Baseline | 7.08 Time (hours.minutes of nightly sleep) | Standard Deviation 0.5 |
| First Stage Melatonin | Actigraphy (Total Sleep Time) | Week 4 | 7.16 Time (hours.minutes of nightly sleep) | Standard Deviation 0.42 |
| First Stage Melatonin | Actigraphy (Total Sleep Time) | Week 8 | 7.06 Time (hours.minutes of nightly sleep) | Standard Deviation 0.45 |
| First Stage Bedtime Bank | Actigraphy (Total Sleep Time) | Baseline | 7.03 Time (hours.minutes of nightly sleep) | Standard Deviation 1.01 |
| First Stage Bedtime Bank | Actigraphy (Total Sleep Time) | Week 4 | 7.01 Time (hours.minutes of nightly sleep) | Standard Deviation 0.38 |
| First Stage Bedtime Bank | Actigraphy (Total Sleep Time) | Week 8 | 7.29 Time (hours.minutes of nightly sleep) | Standard Deviation 0.48 |
Secondary
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
Time frame: Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Baseline, Week 4, and Week 8)
Population: Data Reported on First Stage Randomization of Melatonin vs. Bedtime Bank (Data Collected at: Baseline, Week 4, and Week 8). Data was analyzed based on first stage randomization regardless of whether participants were responders or non-responders.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| First Stage Melatonin | Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Baseline | 37.70 units on a scale | Standard Deviation 7.994 |
| First Stage Melatonin | Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Week 4 | 35.21 units on a scale | Standard Deviation 8.911 |
| First Stage Melatonin | Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Week 8 | 33.74 units on a scale | Standard Deviation 6.723 |
| First Stage Bedtime Bank | Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Baseline | 41.50 units on a scale | Standard Deviation 10.43 |
| First Stage Bedtime Bank | Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Week 4 | 38.79 units on a scale | Standard Deviation 7.052 |
| First Stage Bedtime Bank | Cleveland Adolescent Sleepiness Questionnaire (CASQ) | Week 8 | 38.42 units on a scale | Standard Deviation 8.952 |
Secondary
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
Time frame: Baseline, Week 4, & Week 8 PROMIS Pediatric Item Bank Sleep Disturbance t-scores/SE.
Population: Baseline, Week 4, \& Week 8 PROMIS Pediatric Item Bank Sleep Disturbance t-scores/SE. Data was analyzed based on first stage randomization regardless of whether participants were responders or non-responders.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| First Stage Melatonin | PROMIS Pediatric Item Bank Sleep Disturbance | Week 4 | 59.46 T score | Standard Error 2.5 |
| First Stage Melatonin | PROMIS Pediatric Item Bank Sleep Disturbance | Baseline | 63.37 T score | Standard Error 2.5 |
| First Stage Melatonin | PROMIS Pediatric Item Bank Sleep Disturbance | Week 8 | 56.57 T score | Standard Error 2.7 |
| First Stage Bedtime Bank | PROMIS Pediatric Item Bank Sleep Disturbance | Baseline | 64.160 T score | Standard Error 2.5 |
| First Stage Bedtime Bank | PROMIS Pediatric Item Bank Sleep Disturbance | Week 4 | 59.20 T score | Standard Error 2.5 |
| First Stage Bedtime Bank | PROMIS Pediatric Item Bank Sleep Disturbance | Week 8 | 56.65 T score | Standard Error 2.6 |
Secondary
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
Time frame: Baseline, Week 4, & Week 8-PROMIS Pediatric Item Bank Sleep Related Impairment t-score.
Population: Baseline, Week 4, \& Week 8-PROMIS Pediatric Item Bank Sleep Related Impairment t-score. Data was analyzed based on first stage randomization regardless of whether participants were responders or non-responders.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| First Stage Melatonin | PROMIS Pediatric Item Bank Sleep Related Impairment | Baseline | 58.73 T-score | Standard Error 2.2 |
| First Stage Melatonin | PROMIS Pediatric Item Bank Sleep Related Impairment | Week 4 | 53.87 T-score | Standard Error 2.74 |
| First Stage Melatonin | PROMIS Pediatric Item Bank Sleep Related Impairment | Week 8 | 52.76 T-score | Standard Error 2.7 |
| First Stage Bedtime Bank | PROMIS Pediatric Item Bank Sleep Related Impairment | Baseline | 58.37 T-score | Standard Error 2.3 |
| First Stage Bedtime Bank | PROMIS Pediatric Item Bank Sleep Related Impairment | Week 4 | 53.56 T-score | Standard Error 2.8 |
| First Stage Bedtime Bank | PROMIS Pediatric Item Bank Sleep Related Impairment | Week 8 | 51.62 T-score | Standard Error 2.9 |
Secondary
Urinary Melatonin
The Genway Biotech Melatonin ELISA Kit (San Diego, CA) will allow for the analysis and quantification of endogenous melatonin.
Time frame: Completed once during the baseline week prior to first stage randomization. Results reported by first stage randomization group.
Population: First morning void urinary 6-sulphatoxymelatonin (Urine 6SM). Urine 6SM concentrations were expressed in ng per mg of creatinine (ng/mg Cr) to control for renal function and dilution of urine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| First Stage Melatonin | Urinary Melatonin | 81.90 ng/mg Cr | Standard Deviation 43.67 |
| First Stage Bedtime Bank | Urinary Melatonin | 78.58 ng/mg Cr | Standard Deviation 31.5 |