Feasibility Study of Personalized Trials to Improve Sleep Quality

Sleep Disturbance Clinical Trial

Official title:

Re-engineering Precision Therapeutics Through N-of-1 Trials: Feasibility Study of Personalized Trials to Improve Sleep Quality

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05349188
• Other study ID #: 21-0239
• Secondary ID: R01LM012836
• Status: Completed
• Phase: Phase 1
• Start date: May 11, 2022
• Est. completion date: May 22, 2023

Study information

• Verified date: July 2023
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this pilot study is to assess the feasibility of using N-of-1 methods in a virtual research study of melatonin intervention for poor sleep quality. Participants (N=60) will be sent a Fitbit device and 3 smart pill bottles, with one containing 3 mg of melatonin, one containing 0.5 mg of melatonin, and the final bottle containing a placebo pill. The first two weeks will be a baseline period, where no supplement is assigned, but data are collected, including self-report of sleep quality and duration and accelerometer-derived sleep and activity data. After successful completion of the baseline period, participants will be randomized to six 2-week intervention blocks of a 3 mg dose melatonin, a 0.5 mg dose melatonin, and a placebo. At the end of the trial, participants will be asked to complete the System Usability Scale, a satisfaction survey (electronic or phone/video call if they are non-responders), and participate in a virtual interview (such as over Microsoft Teams or a phone call) to inform feasibility and acceptability of protocol requirements, study materials, and personalized reports.

Description:

The purpose of this pilot study is to assess the feasibility of using N-of-1 methods in a virtual research study; to remotely recruit and enroll participants; to assess the feasibility of using a placebo and to determine the feasibility of the proposed methods used to collect and assess participant adherence and response to a wellness strategy (in this case, melatonin for poor sleep quality). This pilot will help determine if an N-of-1 study design, or what has been termed 'Personalized Trials', can have widespread use in future research and clinical practice to address high public health burdens with a high heterogeneity of response. This pilot study will assess feasibility using a Personalized Trials model to evaluate an individual participant's experience with a wellness strategy for self-reported poor sleep quality. Participants (N=60) will be sent a Fitbit device and 3 smart pill bottles, with one containing 3 mg of melatonin, one containing 0.5 mg of melatonin, and the final bottle containing placebo pills. Participants will be asked several questions a day sent via text message about their sleep quality, as well as their stress, fatigue, concentration, confidence, mood, and pain levels to demonstrate relevant secondary impacts of sleep quality. Participants will also have access to several videos explaining the protocol. The study will take place over the course of 14 weeks. The first two weeks will be a baseline period, where no supplement is assigned, but data are collected, including self-report of sleep quality and duration and accelerometer-derived sleep and activity data. After successful completion of the baseline period, participants will be randomized to six 2-week intervention blocks of a 3 mg dose melatonin, a 0.5 mg dose melatonin, and a placebo. At the end of the 14 weeks, a report containing the individual's observed data will be prepared for each participant and electronically sent to them along with a satisfaction survey (electronic, or phone/video call if they are non-responders).

After the end of the 14-week trial, participants will receive a summary of their observed data in a personalized report. Creating this type of report will help to assess the feasibility of using a N-of-1 trial design through user-acceptability of sleep quality and wellness-related data visualizations, and the ability to choose preferred intervention (if any) based on the data. Participants will be asked to complete the System Usability Scale, a satisfaction survey (electronic or phone/video call if they are non-responders), and participate in a virtual interview (such as over Microsoft Teams or a phone call) to inform feasibility and acceptability of protocol requirements, study materials, and personalized reports.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 22, 2023
• Est. primary completion date: May 16, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Fluent in English

• Ability to take melatonin and a placebo

• Self-report of disrupted sleep symptoms using the Insomnia Symptom Questionnaire (ISQ)

• Owns and can regularly access a smartphone capable of receiving text messages

• Owns and can regularly access an e-mail account

• Lives in the United States

• Agreement to adhere to lifestyle considerations including wearing a Fitbit device day and night and potentially adapting their current melatonin routine to fit the protocol throughout study duration

Exclusion Criteria:

• Age < 18 years old

• Women who are pregnant or breastfeeding

• Individuals diagnosed with depression, seasonal affective disorder, schizophrenia, autoimmune disease, or asthma

• Individuals taking MAO inhibitors or corticosteroids

• Individuals diagnosed with low blood pressure

• Clinical diagnosis of a sleep disorder (e.g., Narcolepsy, Circadian Rhythm Sleep-Wake Disorders, Periodic Limb Movement Disorder, Restless Leg Syndrome, Obstructive Sleep Apnea etc.)

• Deemed unable to complete the study protocol as a result of cognitive impairment, severe medical or mental illness, or active or prior substance abuse

• Participation in shift work (evening/night shifts, early morning shifts, rotating shifts, etc.)

• Pilot or flight attendant with frequent travel across time zones

• Receiving specialty mental health care for insomnia (e.g., cognitive behavioral therapy for insomnia, medications for insomnia)

• Has even been told by a doctor or healthcare provider that it is not safe to take melatonin

• Does not own or cannot regularly access a smartphone capable of receiving text messages

• Does not possess or cannot regularly access an email account

• Lives outside the United States

• Planned surgeries within 6 months from study start date

Related Conditions & MeSH terms

• Dyssomnias
• Parasomnias
• Sleep Disturbance

Intervention

Dietary Supplement:
• 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
Participants will be provided with a smart pill bottle containing a 4-week supply of 0.5 mg melatonin pills.

Other:
• Cellulose placebo pill
Participants will be provided with a smart pill bottle containing a 4-week supply of cellulose placebo pills.

Locations

Country	Name	City	State
United States	Institute of Health System Science	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Northwell Health	Columbia University, National Library of Medicine (NLM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean Within-Subject Difference in Self-Reported Sleep Disturbance.	Participants will rate their sleep disturbance using the Insomnia Severity Index (ISI) administered daily during baseline and intervention periods (14 weeks). Items are rated from 0 to 4, with higher scores indicating greater levels of sleep disturbance. Levels of daily sleep disturbance 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 sleep disturbance over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	Difference in self-reported sleep disturbance will be assessed every two weeks between baseline and intervention periods (14 weeks total).
Other	Within-Subject Difference in Self-Reported Side Effects.	Participant self-reported side effects will be assessed utilizing a weekly survey measure. Number of side effects 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 a count of self-reported side effects in each study period. Side effects over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	Self-reported side effects will be assessed via weekly survey during the baseline assessment period (2 weeks) and during each of the 6 intervention periods (2 weeks each, 12 weeks total).
Other	Within-Subject Difference in Ecological Momentary Assessment (EMA) of Pain.	. Pain will be assessed via 3 daily text message prompts sent at random times throughout the day asking individuals to rate their pain on a scale of 0(low) to 10(high). Levels of EMA pain 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 pain over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	EMA pain 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).
Other	Within-Subject Difference in Ecological Momentary Assessment (EMA) of Mood.	Mood 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(poor) to 10(excellent). Levels of EMA mood 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 mood over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	EMA mood 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).
Other	Within-Subject Difference in Ecological Momentary Assessment (EMA) of Concentration.	Concentration 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 concentration 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 concentration over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	EMA concentration 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).
Other	Within-Subject Difference in Ecological Momentary Assessment (EMA) of Confidence.	Confidence 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 confidence 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 confidence over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	EMA confidence 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).
Other	Within-Subject Difference in Fitbit Device-Recorded Daily Steps.	. Daily step counts will be assessed by a Fitbit device. Daily step counts 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. Daily steps values over the course of the study will be evaluated using Generalized Linear Mixed Model analyses.	Daily steps 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).
Other	Mean participant survey adherence rate.	For each participant of the proportion of surveys measures completed (both daily and weekly surveys) will be calculated. Proportion of days adherent across all participants will be reported with means and standard deviations.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Other	Mean participant ecological momentary assessment (EMA) adherence rate.	For each participant of the proportion of EMA measures completed will be calculated. Proportion of days adherent across all participants will be reported with means and standard deviations.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Primary	Mean System Usability Score (SUS)	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.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Primary	Participant Satisfaction with Personalized Trial Components	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.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Secondary	Within-Participant Difference in Fitbit Device-Recorded Sleep Duration.	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.	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).
Secondary	Mean Within-Subject Difference in Self-Reported Sleep Quality.	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.	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).
Secondary	Within-Subject Difference in Ecological Momentary Assessment (EMA) of Fatigue.	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.	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).
Secondary	Within-Subject Difference in Ecological Momentary Assessment (EMA) of Stress.	Stress 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 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.	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).
Secondary	Mean Fitbit device adherence rate.	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.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Secondary	Mean participant adherence to nightly Melatonin 0.5 mg supplement.	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.	: Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Secondary	Mean participant adherence to nightly Melatonin 3 mg supplement.	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.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).
Secondary	Mean participant adherence to nightly placebo supplement.	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.	Assessed once after the results report has been sent to the participant after completion of the trial (14 weeks from baseline).