Trial Outcomes & Findings for Feasibility Study of Personalized Trials to Improve Sleep Quality (NCT NCT05349188)

Results Overview

The SUS is a validated 10-item questionnaire that asks users to score each item on a Likert scale from Strongly Disagree (rating of 1) to Strongly Agree (rating of 5). The SUS will be presented to the participant as addressing the ease of use, complexity, consistency of the Personalized Trials system as a whole, from recruitment to receipt of the report. Individual results are calculated to arrive at a composite measure out of 100. Participant SUS scores will be averaged together and an overall mean will be reported with standard deviation. Higher scored values correlate to a more usable system, and therefore a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).

Results posted on

2024-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1 Personalized Trial Participants in Group 1 received all three arms of the study in two-week blocks in the following order: 3 mg melatonin, .5 mg melatonin, placebo, placebo, .5 mg melatonin, 3 mg melatonin.	Group 2 Personalized Trial Participants in Group 2 received all three arms of the study in two-week blocks in the following order: placebo, .5 mg melatonin, 3 mg melatonin, 3 mg melatonin, .5 mg melatonin, placebo.
Overall Study STARTED	30	30
Overall Study First Intervention Block (2 Weeks)	30	30
Overall Study Second Intervention Block (2 Weeks)	30	30
Overall Study Third Intervention Block (2 Weeks)	29	30
Overall Study Fourth Intervention Block (2 Weeks)	29	30
Overall Study Fifth Intervention Block (2 Weeks)	29	30
Overall Study Sixth Intervention Block (2 Weeks)	29	30
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1 Personalized Trial Participants in Group 1 received all three arms of the study in two-week blocks in the following order: 3 mg melatonin, .5 mg melatonin, placebo, placebo, .5 mg melatonin, 3 mg melatonin.	Group 2 Personalized Trial Participants in Group 2 received all three arms of the study in two-week blocks in the following order: placebo, .5 mg melatonin, 3 mg melatonin, 3 mg melatonin, .5 mg melatonin, placebo.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Feasibility Study of Personalized Trials to Improve Sleep Quality

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 Personalized Trial n=30 Participants Participants in Group 1 received all three arms of the study in two-week blocks in the following order: 3 mg melatonin, .5 mg melatonin, placebo, placebo, .5 mg melatonin, 3 mg melatonin.	Group 2 Personalized Trial n=30 Participants Participants in Group 2 received all three arms of the study in two-week blocks in the following order: placebo, .5 mg melatonin, 3 mg melatonin, 3 mg melatonin, .5 mg melatonin, placebo.	Total n=60 Participants Total of all reporting groups
Age, Continuous	42.9 years STANDARD_DEVIATION 13.1 • n=5 Participants	39.4 years STANDARD_DEVIATION 12.3 • n=7 Participants	41.1 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex/Gender, Customized Female	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Sex/Gender, Customized Male	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Sex/Gender, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).

Population: Pre-specified to report results at the whole sample level. Though the study utilizes two groups with two treatment orders, this is done to counter-balance the presentation of treatments (3 mg melatonin, .5 mg melatonin, and placebo). Of the 60 participants enrolled in the trial, all were sent the SUS to evaluate the feasibility and acceptability of the trial. Completed survey measures were received for 57 of the 60 (95.0%) participants who were offered the outcome measures.

The SUS is a validated 10-item questionnaire that asks users to score each item on a Likert scale from Strongly Disagree (rating of 1) to Strongly Agree (rating of 5). The SUS will be presented to the participant as addressing the ease of use, complexity, consistency of the Personalized Trials system as a whole, from recruitment to receipt of the report. Individual results are calculated to arrive at a composite measure out of 100. Participant SUS scores will be averaged together and an overall mean will be reported with standard deviation. Higher scored values correlate to a more usable system, and therefore a better outcome.

Outcome measures

Outcome measures
Measure	All Participants n=57 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Mean System Usability Score (SUS)	76.27 score on a scale Standard Deviation 17.09	—	—	—

PRIMARY outcome

Timeframe: Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).

Population: Pre-specified to report results at the whole sample level. Though the study utilizes two groups with two treatment orders, this is done to counter-balance the presentation of treatments (3 mg melatonin, .5 mg melatonin, and placebo). Of the 60 participants enrolled in the trial, all were sent a satisfaction survey to evaluate the feasibility and acceptability of the trial. Completed survey measures were received for 57 of the 60 (95.0%) participants who were offered the outcome measures.

Participants will rate their satisfaction with the Personalized N-of-1 Trial overall and with individual elements of the trial in a satisfaction survey administered following the baseline and intervention periods (14 weeks). Means and standard deviations will be reported for each element of satisfaction. Participants will rate their satisfaction on a scale of 1 to 5, with higher scores indicating greater levels of satisfaction.

Outcome measures

Outcome measures
Measure	All Participants n=57 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Participant Satisfaction With Personalized Trial Components "Your Personalized Trial to Improve Sleep Quality."	4.04 score on a scale Standard Deviation 1.19	—	—	—
Participant Satisfaction With Personalized Trial Components "Video explanations and demonstrations of study devices and procedures."	4.40 score on a scale Standard Deviation .75	—	—	—
Participant Satisfaction With Personalized Trial Components "Text messaging for reminders."	3.67 score on a scale Standard Deviation 1.42	—	—	—
Participant Satisfaction With Personalized Trial Components "Text messaging for survey questions."	3.47 score on a scale Standard Deviation 1.48	—	—	—
Participant Satisfaction With Personalized Trial Components "Use of the Fitbit to track your activity and sleep."	4.58 score on a scale Standard Deviation .94	—	—	—
Participant Satisfaction With Personalized Trial Components "Presentation of your results."	4.51 score on a scale Standard Deviation .89	—	—	—

SECONDARY outcome

Timeframe: Nightly sleep duration will be assessed consistently via Fitbit device during the baseline assessment period (2 weeks) and during each of the 6 intervention periods (2 weeks each, 12 weeks total).

Population: Of the 60 enrolled participants, 55 (91.7%) participants had sufficient Fitbit data to include in analyses.

Nightly sleep duration will be assessed by a Fitbit wearable device. Sleep duration will be aggregated within the baseline assessment period and in each of the intervention periods (3 mg melatonin, 0.5 mg melatonin, placebo) to generate an overall mean and standard deviation for each period. Sleep duration values over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg n=55 Participants Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg n=55 Participants Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill n=55 Participants Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Within-Participant Difference in Fitbit Device-Recorded Sleep Duration.	399 minutes per night Standard Deviation 53	402 minutes per night Standard Deviation 61	398 minutes per night Standard Deviation 54	398 minutes per night Standard Deviation 59

SECONDARY outcome

Timeframe: Daily sleep quality will be assessed daily via survey during the baseline assessment period (2 weeks) and during each of the 6 intervention periods (2 weeks each).

Population: Of the 60 enrolled participants, 55 (91.7%) participants had sufficient sleep quality data during the baseline assessment, melatonin .5 mg, and placebo periods, and 54 (90.0%) participants had sufficient sleep quality data during the melatonin 3 mg period to include in analyses.

Participants will rate their sleep disturbance using a modified version of the Consensus Sleep Diary administered daily during baseline and intervention periods (14 weeks). Participants will be asked to rate their sleep on a 5-point scale rated from "very poor" to "very good". Levels of daily sleep quality will be aggregated within the baseline assessment period and in each of the intervention periods (3 mg melatonin, 0.5 mg melatonin, placebo) to generate an overall mean and standard deviation for each period, with higher scores indicating better sleep quality. Changes in sleep quality over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg n=54 Participants Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg n=55 Participants Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill n=55 Participants Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Mean Within-Subject Difference in Self-Reported Sleep Quality.	3.13 score on a scale per day Standard Deviation .64	3.35 score on a scale per day Standard Deviation .56	3.44 score on a scale per day Standard Deviation .55	3.38 score on a scale per day Standard Deviation .53

SECONDARY outcome

Timeframe: EMA fatigue will be assessed 3 times daily via text message during the baseline assessment period (2 weeks) and during each of the 6 intervention periods (2 weeks each, 12 weeks total).

Population: Of the 60 enrolled participants, 55 (91.7%) participants had sufficient EMA data during the baseline assessment, melatonin .5 mg, and placebo periods, and 54 (90.0%) participants had sufficient EMA data during the melatonin 3 mg period to include in analyses.

Fatigue will be assessed via 3 daily text message prompts sent at random times throughout the day asking individuals to rate their fatigue on a scale of 0(low) to 10(high). Levels of EMA fatigue will be aggregated within the baseline assessment period and in each of the intervention periods (3 mg melatonin, 0.5 mg melatonin, placebo) to generate an overall mean and standard deviation for each period. Changes in EMA fatigue over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg n=54 Participants Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg n=55 Participants Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill n=55 Participants Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Within-Subject Difference in Ecological Momentary Assessment (EMA) of Fatigue.	3.85 units on a scale per period Standard Deviation 1.95	3.58 units on a scale per period Standard Deviation 1.98	3.49 units on a scale per period Standard Deviation 2.07	3.44 units on a scale per period Standard Deviation 2.00

SECONDARY outcome

Timeframe: EMA stress will be assessed 3 times daily via text message during the baseline assessment period (2 weeks) and during each of the 6 intervention periods (2 weeks each, 12 weeks total).

Population: Of the 60 enrolled participants, 55 (91.7%) participants had sufficient EMA data during the baseline assessment, melatonin .5 mg, and placebo periods, and 54 (90.0%) participants had sufficient EMA data during the melatonin 3 mg period to include in analyses.

Stress will be assessed via 3 daily text message prompts sent at random times throughout the day asking individuals to rate their stress on a scale of 0(low) to 10(high). Levels of EMA stress will be aggregated within the baseline assessment period and in each of the intervention periods (3 mg melatonin, 0.5 mg melatonin, placebo) to generate an overall mean and standard deviation for each period. Changes in EMA stress over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg n=54 Participants Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg n=55 Participants Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill n=55 Participants Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Within-Subject Difference in Ecological Momentary Assessment (EMA) of Stress.	3.19 units on a scale per period Standard Deviation 1.86	3.34 units on a scale per period Standard Deviation 1.78	3.29 units on a scale per period Standard Deviation 1.86	3.33 units on a scale per period Standard Deviation 1.96

SECONDARY outcome

Timeframe: Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).

Population: Pre-specified to report results at the whole sample level. Of the 60 enrolled participants, 55 (91.7%) had sufficient Fitbit data across the 98 day study to include in analyses.

For each participant, the proportion of days where the Fitbit device was worn will be calculated. Proportion of days where the Fitbit device was worn across all participants will be reported with means and standard deviations.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Mean Fitbit Device Adherence Rate.	88.01 days Standard Deviation 3.00	—	—	—

SECONDARY outcome

Timeframe: Assessed across the two 14-day treatment periods (28 days total).

Population: Pre-specified to report results at the whole sample level. Of the 60 enrolled participants, 55 (91.7%) had sufficient supplement adherence data across each 28 day study period (3 mg melatonin, .5 mg melatonin, and placebo) to include in analyses.

For each participant, the proportion of days where the melatonin 0.5 mg supplement was administered will be calculated. Proportion of days adherent across all participants will be reported with means and standard deviations.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Mean Participant Adherence to Nightly Melatonin 0.5 mg Supplement.	21.82 days Standard Deviation 2.19	—	—	—

SECONDARY outcome

Timeframe: Assessed across the two 14-day treatment periods (28 days total).

Population: Pre-specified to report results at the whole sample level. Of the 60 enrolled participants, 55 (91.7%) had sufficient supplement adherence data across each 28 day study period (3 mg melatonin, .5 mg melatonin, and placebo) to include in analyses.

For each participant, the proportion of days where the melatonin 3 mg supplement was administered will be calculated. Proportion of days adherent across all participants will be reported with means and standard deviations.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Mean Participant Adherence to Nightly Melatonin 3 mg Supplement.	21.78 days Standard Deviation 2.20	—	—	—

SECONDARY outcome

Timeframe: Assessed across the two 14-day treatment periods (28 days total).

Population: Pre-specified to report results at the whole sample level. Of the 60 enrolled participants, 55 (91.7%) had sufficient supplement adherence data across each 28 day study period (3 mg melatonin, .5 mg melatonin, and placebo) to include in analyses.

For each participant, the proportion of days where the placebo supplement was administered will be calculated. Proportion of days adherent across all participants will be reported with means and standard deviations.

Outcome measures

Outcome measures
Measure	All Participants n=55 Participants Participants in both treatment order groups are combined for analyses of primary and secondary outcomes.	Melatonin 3 mg Individuals will receive a kit with medication adherence devices containing melatonin 3 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 3mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 3 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 3 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 3 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	Melatonin 0.5 mg Individuals will receive a kit with medication adherence devices containing melatonin 0.5 mg in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the 0.5 mg of melatonin. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive melatonin 0.5 mg, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The melatonin 0.5 mg intervention will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Melatonin 0.5 mg: Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo Pill Individuals will receive a kit with medication adherence devices containing the placebo pills in one of three smart electronic pill bottles labeled "A," "B," and "C." Participants will not be aware which of the pill bottles contains the placebo. Participants will be randomized to take pills in 6 alternating intervention periods 2 weeks in length. During periods where participants were randomized to receive the placebo, they will receive a nightly text notification 1 hour before bed instructing them to take a pill from the corresponding smart pill bottle. The placebo will be administered in 2 intervention periods each 2 weeks in length (4 weeks total). Cellulose placebo pill: Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
Mean Participant Adherence to Nightly Placebo Supplement.	21.53 days Standard Deviation 2.23	—	—	—

Adverse Events

3 mg Melatonin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

.5 mg Melatonin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	3 mg Melatonin n=60 participants at risk Dietary Supplement: Melatonin 3 mg Participants provided with a smart pill bottle containing a 4-week supply of 3 mg melatonin pills.	.5 mg Melatonin n=60 participants at risk Dietary Supplement: Melatonin 0.5 mg Participants provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.	Placebo n=60 participants at risk Cellulose placebo pill Participants provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.
General disorders Headache	5.0% 3/60 • Number of events 8 • Data for each participant were collected over a 14-week period (2-week baseline and 12-week intervention). Systematic assessment was conducted via a daily survey sent to participants asking if they are experiencing any side effects.	0.00% 0/60 • Data for each participant were collected over a 14-week period (2-week baseline and 12-week intervention). Systematic assessment was conducted via a daily survey sent to participants asking if they are experiencing any side effects.	0.00% 0/60 • Data for each participant were collected over a 14-week period (2-week baseline and 12-week intervention). Systematic assessment was conducted via a daily survey sent to participants asking if they are experiencing any side effects.

Additional Information

Dr. Mark Butler, PhD

Northwell Health

Phone: 908-414-0238

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place