Trial Outcomes & Findings for Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance (NCT NCT02156271)

Results Overview

The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects. Sleep latency is defined as the length of time it takes from lying down for the night until sleep onset.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

75 participants

Primary outcome timeframe

Day 89-90

Results posted on

2015-07-28

Participant Flow

A total of 75 subjects signed consent and were enrolled in the study. Of these, 23 (31%) failed to qualify to participate in the study based on screening assessments, 12 (16%) withdrew consent prior to randomization, and 4 (5%) dropped out before randomization. As a result, 39 subjects were randomized.

Participant milestones

Participant milestones
Measure	Ramelteon Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo 15 subjects will be randomized to receive the placebo placebo
Overall Study STARTED	26	13
Overall Study COMPLETED	22	10
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Ramelteon Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo 15 subjects will be randomized to receive the placebo placebo
Overall Study Physician Decision	4	3

Baseline Characteristics

Mechanisms of Sleep Latency and Health: The Effect of a Melatonin Receptor Agonist in Inflammation and Insulin Resistance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	13 Participants n=7 Participants	39 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	8 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	13 participants n=7 Participants	39 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 89-90

The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects. Sleep latency is defined as the length of time it takes from lying down for the night until sleep onset.

Outcome measures

Outcome measures
Measure	Ramelteon n=22 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=10 Participants 15 subjects will be randomized to receive the placebo placebo
Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary)	29.7 minutes Standard Deviation 21.7	24.8 minutes Standard Deviation 15.2

PRIMARY outcome

Timeframe: Day 89-90

Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured.

Outcome measures

Outcome measures
Measure	Ramelteon n=22 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=10 Participants 15 subjects will be randomized to receive the placebo placebo
Mean Latency to Persistent Sleep (LPS) Via Polysomnography	19.2 minutes Standard Deviation 11.3	48.6 minutes Standard Deviation 33.0

PRIMARY outcome

Timeframe: Baseline, Day 30, Day 60, Day 89-90

Population: Data was not collected, and therefore not analyzed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: baseline

Subjects completed component 2 of the PSQI questionnaire. Component 2 asks questions about sleep latency and is scored on a scale from 0 (better) to 3 (worse).

Outcome measures

Outcome measures
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo
Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI)	2.5 units on a scale Standard Deviation 0.7	2.8 units on a scale Standard Deviation 0.6

PRIMARY outcome

Timeframe: day 89 - 90

Subjects completed component 2 of the PSQI questionnaire. Component 2 asks questions about sleep latency and is scored on a scale from 0 (better) to 3 (worse).

Outcome measures

Outcome measures
Measure	Ramelteon n=22 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=10 Participants 15 subjects will be randomized to receive the placebo placebo
Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI)	1.72 units on a scale Standard Deviation 0.9	0.93 units on a scale Standard Deviation 1.1

PRIMARY outcome

Timeframe: Baseline

Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured.

Outcome measures

Outcome measures
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo
Mean Latency to Persistent Sleep (LPS) Via Polysomnography	41.0 minutes Standard Deviation 25.4	46.3 minutes Standard Deviation 20.1

PRIMARY outcome

Timeframe: Baseline

The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects.

Outcome measures

Outcome measures
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo
Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary)	41.3 minutes Standard Deviation 32.9	38.8 minutes Standard Deviation 19.8

SECONDARY outcome

Timeframe: Day -1-0, Day 89-90

Population: Data was not collected, and therefore not analyzed.

Change in sleep time will be determined by PSG.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 89-90

Outcome measures

Outcome measures
Measure	Ramelteon n=22 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=10 Participants 15 subjects will be randomized to receive the placebo placebo
Inflammatory Biomarkers C-reactive Protein (CRP)	11.9 ng/mL Standard Deviation 12.7	7.3 ng/mL Standard Deviation 28.1

SECONDARY outcome

Timeframe: Day 89-90

Outcome measures

Outcome measures
Measure	Ramelteon n=22 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=10 Participants 15 subjects will be randomized to receive the placebo placebo
Interleukin 6 (IL-6)	2.2 pg/mL Standard Deviation 1.4	1.3 pg/mL Standard Deviation 1.0

SECONDARY outcome

Timeframe: Day 89-90

In each subject, an insulin resistance score based on Homeostasis Model Assessment (HOMA-IR) was estimated at day 89-90. Formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance).

Outcome measures

Outcome measures
Measure	Ramelteon n=22 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=10 Participants 15 subjects will be randomized to receive the placebo placebo
Insulin Resistance (IR)	12.6 HOMA-IR value Standard Deviation 12.2	7.9 HOMA-IR value Standard Deviation 6.6

SECONDARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo
Inflammatory Biomarkers C-reactive Protein (CRP)	11.8 mg/L Standard Deviation 16.9	26.1 mg/L Standard Deviation 38.9

SECONDARY outcome

Timeframe: Baseline

In each subject, an insulin resistance score based on Homeostasis Model Assessment (HOMA-IR) was estimated at baseline. Formula: fasting plasma glucose (mmol/l) times fasting serum insulin (mU/l) divided by 22.5. Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate low insulin sensitivity (insulin resistance).

Outcome measures

Outcome measures
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo
Insulin Resistance (IR)	16.9 HOMA-IR value Standard Deviation 10.8	12.4 HOMA-IR value Standard Deviation 9.2

SECONDARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	Ramelteon n=26 Participants Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 Participants 15 subjects will be randomized to receive the placebo placebo
Interleukin 6 (IL-6)	1.6 pg/mL Standard Deviation 1.1	2.5 pg/mL Standard Deviation 2.4

Adverse Events

Ramelteon

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ramelteon n=26 participants at risk Subjects will take ramelteon 8mg one time daily 30 minutes before bedtime with approximately 8 ounces of water. Subjects have a 2 out of 3 chance of receiving ramelteon. ramelteon	Placebo n=13 participants at risk 15 subjects will be randomized to receive the placebo placebo
Nervous system disorders Dizziness	3.8% 1/26	0.00% 0/13
Psychiatric disorders Depression	3.8% 1/26	0.00% 0/13
General disorders Body Aches	0.00% 0/26	7.7% 1/13
Nervous system disorders Drowsiness	15.4% 4/26	0.00% 0/13
Musculoskeletal and connective tissue disorders Back Ache	0.00% 0/26	7.7% 1/13
Gastrointestinal disorders Diarrhea	0.00% 0/26	7.7% 1/13
Musculoskeletal and connective tissue disorders Sore Ankle	3.8% 1/26	0.00% 0/13
General disorders cold symptoms	3.8% 1/26	0.00% 0/13
Musculoskeletal and connective tissue disorders Knee Pain	3.8% 1/26	0.00% 0/13
Musculoskeletal and connective tissue disorders dislocated shoulder	3.8% 1/26	0.00% 0/13

Additional Information

Dr. Andrew Krystal

Duke University Medical Center

Phone: 919-681-8742

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place