Trial Outcomes & Findings for The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder (NCT NCT03715465)

NCT ID: NCT03715465

Last Updated: 2022-11-25

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 44 participants
• Primary outcome timeframe: After 4 weeks of melatonin therapy
• Results posted on: 2022-11-25

Participant Flow

44 participants total were enrolled in this trial, 4 of whom withdrew before randomization to the arms.

Participant milestones

Measure	Measured DLMO 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO 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. Melatonin 0.5 MG: Melatonin tablet
Overall Study STARTED	20	20
Overall Study COMPLETED	19	18
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Measured DLMO 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO 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. Melatonin 0.5 MG: Melatonin tablet
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Baseline DLMO was not calculable for 5 participants in the E-DLMO group

Baseline characteristics by cohort

Measure	Measured DLMO n=20 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=20 Participants 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. Melatonin 0.5 MG: Melatonin tablet	Total n=40 Participants Total of all reporting groups
Age, Continuous	25.45 years STANDARD_DEVIATION 6.19 • n=20 Participants	26.70 years STANDARD_DEVIATION 5.62 • n=20 Participants	26.08 years STANDARD_DEVIATION 5.87 • n=40 Participants
Sex: Female, Male Female	16 Participants n=20 Participants	13 Participants n=20 Participants	29 Participants n=40 Participants
Sex: Female, Male Male	4 Participants n=20 Participants	7 Participants n=20 Participants	11 Participants n=40 Participants
Race/Ethnicity, Customized White/Caucasian	11 Participants n=20 Participants	18 Participants n=20 Participants	29 Participants n=40 Participants
Race/Ethnicity, Customized Black/African American	4 Participants n=20 Participants	0 Participants n=20 Participants	4 Participants n=40 Participants
Race/Ethnicity, Customized Asian	4 Participants n=20 Participants	0 Participants n=20 Participants	4 Participants n=40 Participants
Race/Ethnicity, Customized I have two or more racial backgrounds	1 Participants n=20 Participants	2 Participants n=20 Participants	3 Participants n=40 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	19 Participants n=20 Participants	19 Participants n=20 Participants	38 Participants n=40 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=20 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants
Race/Ethnicity, Customized Ethnicity Unknown	1 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Region of Enrollment United States	20 Participants n=20 Participants	20 Participants n=20 Participants	40 Participants n=40 Participants
Dim Light Melatonin Onset	22.90 Clock time in hours STANDARD_DEVIATION 2.23 • n=20 Participants • Baseline DLMO was not calculable for 5 participants in the E-DLMO group	22.55 Clock time in hours STANDARD_DEVIATION 1.52 • n=15 Participants • Baseline DLMO was not calculable for 5 participants in the E-DLMO group	22.75 Clock time in hours STANDARD_DEVIATION 1.93 • n=35 Participants • Baseline DLMO was not calculable for 5 participants in the E-DLMO group

PRIMARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: Data were not analyzed for 2 participants in the Measured DLMO group and 7 participants in the Estimated DLMO group due to missing or incalculable DLMO data at one or both of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=13 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Time of Dim Light Melatonin Onset (DLMO) at 4 Weeks	-1.23 Hours Standard Deviation 1.53	-1.58 Hours Standard Deviation 1.30

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

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.

Outcome measures

Measure	Measured DLMO n=19 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
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 per diary	0.41 Hours Standard Deviation 0.79	0.65 Hours Standard Deviation 0.99
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 per actigraphy	0.63 Hours Standard Deviation 0.79	0.66 Hours Standard Deviation 1.00

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

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.

Outcome measures

Measure	Measured DLMO n=19 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Sleep Onset Time at 4 Weeks change in sleep onset time per diary	-1.73 Hours Standard Deviation 1.10	-1.84 Hours Standard Deviation 1.40
Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Sleep Onset Time at 4 Weeks change in sleep onset time per actigraphy	-1.58 Hours Standard Deviation 1.11	-1.63 Hours Standard Deviation 1.47

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

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.

Outcome measures

Measure	Measured DLMO n=19 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Sleep Offset Time at 4 Weeks change in sleep offset time per diary	-1.61 Hours Standard Deviation 0.98	-1.96 Hours Standard Deviation 0.96
Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Diary Parameters - Sleep Offset Time at 4 Weeks change in sleep offset time per actigraphy	-1.15 Hours Standard Deviation 0.89	-1.45 Hours Standard Deviation 1.18

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

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.

Outcome measures

Measure	Measured DLMO n=19 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Onset Latency at 4 Weeks change in sleep onset latency per diary	-14.35 Minutes Standard Deviation 32.61	-10.21 Minutes Standard Deviation 17.25
Change From Baseline Score on Wrist Actigraphy and Self-Report Diary Sleep Onset Latency at 4 Weeks change in sleep onset latency per actigraphy	-9.75 Minutes Standard Deviation 36.83	-0.53 Minutes Standard Deviation 25.19

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Epworth Sleepiness Scale at 4 Weeks	-1.61 score on a scale Standard Deviation 2.75	-0.78 score on a scale Standard Deviation 3.80

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Multidimensional Fatigue Inventory at 4 Weeks	-3.78 score on a scale Standard Deviation 8.73	-6.50 score on a scale Standard Deviation 10.43

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: 10 participants in the Measured DLMO and 5 participants in the Estimated DLMO group did not complete this measure due to an error in data collection procedures.

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.

Outcome measures

Measure	Measured DLMO n=9 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=13 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Sheehan Disability Scale at 4 Weeks	-0.33 score on a scale Standard Deviation 4.92	-5.85 score on a scale Standard Deviation 6.63

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Patient Health Questionnaire-9 at 4 Weeks	0.28 Score on a Questionnaire Standard Deviation 2.63	-0.39 Score on a Questionnaire Standard Deviation 3.53

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on Generalized Anxiety Disorder-7 Scale at 4 Weeks	1.11 units on a scale Standard Deviation 3.03	-0.50 units on a scale Standard Deviation 2.79

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO and one participant in the Estimated DLMO group were not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=17 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on the Pittsburgh Sleep Quality Index at 4 Weeks	1.61 score on a scale Standard Deviation 2.87	-0.59 score on a scale Standard Deviation 3.74

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on the Morningness Eveningness Questionnaire at 4 Weeks	4.89 score on a scale Standard Deviation 4.73	12.17 score on a scale Standard Deviation 9.65

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on the PROMIS-Sleep Disturbance Scale at 4 Weeks	-3.56 score on a scale Standard Deviation 6.28	-5.94 score on a scale Standard Deviation 5.85

SECONDARY outcome

Timeframe: After 4 weeks of melatonin therapy

Population: One participant in the Measured DLMO group was not included in the analysis because they did not complete the measure at one of the time points.

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.

Outcome measures

Measure	Measured DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=18 Participants 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. Melatonin 0.5 MG: Melatonin tablet
Change From Baseline Score on the PROMIS-Sleep Related Impairment Scale at 4 Weeks	-3.94 score on a scale Standard Deviation 5.25	-6.11 score on a scale Standard Deviation 7.75

Adverse Events

Measured DLMO

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Estimated DLMO

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Measured DLMO n=20 participants at risk 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. Melatonin 0.5 MG: Melatonin tablet Dim Light Melatonin Onset (salivary): Test to determine the time of melatonin onset in saliva under dim light conditions	Estimated DLMO n=20 participants at risk 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. Melatonin 0.5 MG: Melatonin tablet
Psychiatric disorders Irritability	0.00% 0/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
Psychiatric disorders Somnolence	55.0% 11/20 • 4 weeks.	45.0% 9/20 • 4 weeks.
Skin and subcutaneous tissue disorders Rash	10.0% 2/20 • 4 weeks.	0.00% 0/20 • 4 weeks.
Ear and labyrinth disorders Hypoacusis	0.00% 0/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
Eye disorders Eye irritation	0.00% 0/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
Gastrointestinal disorders Gingival bleeding	0.00% 0/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
General disorders Decreased appetite	10.0% 2/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
Nervous system disorders Dizziness	0.00% 0/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
Nervous system disorders Headaches	20.0% 4/20 • 4 weeks.	20.0% 4/20 • 4 weeks.
Nervous system disorders Migraine	10.0% 2/20 • 4 weeks.	0.00% 0/20 • 4 weeks.
Psychiatric disorders Anxiety	0.00% 0/20 • 4 weeks.	20.0% 4/20 • 4 weeks.
Psychiatric disorders Depression	0.00% 0/20 • 4 weeks.	10.0% 2/20 • 4 weeks.
Psychiatric disorders Insomnia	15.0% 3/20 • 4 weeks.	20.0% 4/20 • 4 weeks.

Additional Information

Leslie Swanson

University of Michigan

Phone: 734-764-2242

Email: lmswan@med.umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place