The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder

Study Overview
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Brief Summary
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This study will test whether measuring the circadian clock during treatment of delayed sleep-wake phase disorder results in greater improvements in sleep compared to estimating the circadian clock.

Detailed Description
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The study is a randomized, controlled, parallel double-blind 4-week trial of 0.5 mgs of exogenous melatonin timed to either 3 h before actual dim light melatonin onset (DLMO) based on in-home measurement (M-DLMO, n = 25) or 3 h before DLMO estimated at 2 h before average sleep onset time based on actigraphy and sleep diary (E-DLMO, n = 25) in adult participants with delayed sleep-wake phase disorder. All participants will receive melatonin 0.5 mgs. Outcomes include change in DLMO, subjective and objective sleep parameters, and daytime symptoms. As of January 7, 2020, the Insomnia Severity Index was removed from the IRB-approved protocol. No data were collected for this measure.

Official Title
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The Clinical Utility of DLMO in the Treatment of Delayed Sleep-Wake Phase Disorder: A Randomized Trial

Conditions
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Delayed Sleep Phase Syndrome

Intervention / Treatment
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* Drug: Melatonin 0.5 MG
* Other: Dim Light Melatonin Onset (salivary)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet diagnostic criteria for delayed sleep wake phase disorder Female participants of childbearing potential must agree to use a reliable method of contraception from the screening visit until 4 weeks after the study has completed. Exclusion Criteria: Hypersensitivity to melatonin or any other component of the product Sleep disorder other than delayed sleep wake phase disorder Medical and psychiatric conditions that may influence sleep or be affected by melatonin Current use of medications which may have interactions with melatonin Pregnancy or breastfeeding Routine night shift work Past month travel or planned travel during the study across more than one time zone Use of melatonin in the past month Current use of medications that may interfere with the measurement of melatonin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Estimated DLMO<br>Four weeks (28 days) of nightly melatonin 0.5 mg fast dissolve tablets timed to be administered 3 hours before estimated dim light melatonin onset. | Drug: Melatonin 0.5 MG<br>* Melatonin tablet<br>|
| Experimental: Measured DLMO<br>Four weeks (28 days) of nightly melatonin 0.5 mg fast dissolve tablets timed to be administered 3 hours before measured dim light melatonin onset. | Drug: Melatonin 0.5 MG<br>* Melatonin tablet<br>Other: Dim Light Melatonin Onset (salivary)<br>* Test to determine the time of melatonin onset in saliva under dim light conditions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Time of Dim Light Melatonin Onset (DLMO) at 4 Weeks | Onset of melatonin in dim light conditions as measured in saliva (also called DLMO). Time of DLMO is measured in clock time and change in time of DLMO is measured in hours. The change score is calculated as time at 4 weeks minus baseline time. Thus, positive scores indicate a shift towards a later onset of melatonin and negative scores indicate a shift towards an earlier onset of melatonin. | After 4 weeks of melatonin therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Total Sleep Time at 4 Weeks | Change in total sleep time is measured in hours. The change score is calculated by subtracting total sleep time at 4 weeks from total sleep time at baseline. Thus, positive scores indicate an increase in total sleep time, whereas negative scores indicate a decrease in total sleep time. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Sleep Onset Time at 4 Weeks | Sleep onset time is measured in clock time and reflects time of falling asleep. The change score is calculated as time at 4 weeks minus baseline time. Thus, positive scores indicate a shift towards a later fall asleep time and negative scores indicate a shift towards an earlier fall asleep time. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Sleep Offset Time at 4 Weeks | Sleep offset time is measured in clock time and reflects time of waking for the day. The change score is calculated as time at 4 weeks minus baseline time. Thus, positive scores indicate a shift towards a later wake time and negative scores indicate a shift towards an earlier wake time. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Onset Latency at 4 Weeks | Length of time to sleep onset latency in minutes (reflects time to fall asleep). The change score is calculated as time at 4 weeks minus baseline time. Thus, a negative scores indicate a reduction in time to fall asleep, whereas positive scores indicate an increase in time to fall asleep. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Epworth Sleepiness Scale at 4 Weeks | Self-report of daytime sleepiness. Scores range from 0 to 24. Scores of 10 or higher indicate excessive daytime sleepiness. The change score is calculated as score at 4 weeks minus baseline score.Thus, positive scores indicate an increase in sleepiness, whereas negative scores indicate a reduction in sleepiness. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Multidimensional Fatigue Inventory at 4 Weeks | Self-report of daytime fatigue. Scores range from 20-100; higher scores indicate more fatigue. The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate an increase in fatigue, whereas negative scores indicate a reduction in fatigue. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Sheehan Disability Scale at 4 Weeks | Self-report of functional impairment in works/school, social, and family life. Scores range from 0-30; higher scores indicate more impairment. The change score is calculated as time at 4 weeks minus baseline time Thus, positive scores indicate increased impairment, whereas negative scores indicate a reduction in impairment. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Patient Health Questionnaire-9 at 4 Weeks | Self-report of depression symptoms. Scores range from 0-27; higher scores indicate more severe depression. The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate an increase in depression, whereas negative scores indicate a reduction in depression. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on Generalized Anxiety Disorder-7 Scale at 4 Weeks | Self-report of generalized anxiety symptoms. Scores range from 0-21; higher scores indicate more severe anxiety. The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate an increase in anxiety, whereas negative scores indicate a reduction in anxiety. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on the Pittsburgh Sleep Quality Index at 4 Weeks | Self-report of sleep quality. Seven subscale scores are summed to obtain a global score. Global scores range from 0 to 21; scores of 5 or higher indicate poor sleep quality. The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate a worsening of sleep quality, whereas negative scores indicate an improvement in sleep quality. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on the Morningness Eveningness Questionnaire at 4 Weeks | Self-report of chronotype. Scores range from 16-86. Lower scores indicate more eveningness.The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate a shift towards more morningness, whereas negative scores indicate a shift towards more eveningness. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on the PROMIS-Sleep Disturbance Scale at 4 Weeks | Self-report of sleep disturbances. Scores range from 8-40. Higher scores indicate greater sleep disturbance. The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate a worsening of sleep disturbance, whereas negative scores indicate an improvement in sleep disturbance. | After 4 weeks of melatonin therapy | 
| Change From Baseline Score on the PROMIS-Sleep Related Impairment Scale at 4 Weeks | Self-report of impairment related to sleep. Scores range from 8-40. Higher scores indicate greater impairment due to sleep. The change score is calculated as score at 4 weeks minus baseline score. Thus, positive scores indicate an increase in impairment due to sleep, whereas negative scores indicate a reduction in impairment due to sleep. | After 4 weeks of melatonin therapy |