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

Phase 4

Completed

Brief Summary: The purpose of this study is to help scientist better understand the effect of a 12-week single daily evening dose of ramelteon (Rozerem ©), a drug that has been approved by the U. S. Food and Drug Administration (FDA) for the treatment of insomnia (trouble falling asleep or staying asleep). The study will measure levels of inflammation, fasting insulin and fasting glucose (sugar) in subjects who are taking either ramelteon (8 mg) or placebo.

Recruitment & Eligibility

Inclusion Criteria

At screening visit:

aged 18-65
nonsmokers
for women: oral contraceptive (OC) or hormone replacement therapy (HRT) nonusers

To schedule the baseline PSG (Visit 2), subjects must meet the following inclusion criteria:

ages 18-65 inclusive;
PSQI-Component 2 (sleep latency) score of greater than 1;
non-smoker (e.g., less than 20 cigarettes in the past 5 years);
habitual bedtime between 8:30 pm and midnight
For premenopausal women:
- regular menstrual cycles determined by Framingham Study criteria;
- not pregnant and no history of oral contraceptive (OC) usage in last 6-months.
For postmenopausal women:
- no recent (< 6 months) use of Hormone Replacement Therapy (HRT)
- no surgical menopause

Exclusion Criteria

positive urine drug screen
Potential subjects with hypersensitivity to ramelteon or any components of the formulation will be excluded from participation.
Given that ramelteon should not be used by individuals with severe hepatic impairment, or in patients in combination with fluvoxamine, individuals who report liver problem or use of fluvox will be excluded.
use of rifampin (Rifadin ©); ketoconazole (Nizora ©l); or fluconazole (Diflucan ©).
Ramelteon has not been studied in children or adolescents, and the effects in these populations are unknown, thus only individuals above 18 years will participate.

Arm && Interventions

Group	Intervention	Description
placebo	placebo	15 subjects will be randomized to receive the placebo
ramelteon	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.

Primary Outcome Measures

Name	Time	Method
Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary)	Baseline	The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects.
Mean Latency to Persistent Sleep (LPS) Via Polysomnography	Baseline	Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured.
Change in Metabolic Syndrome (MetSyn)	Baseline, Day 30, Day 60, Day 89-90
Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI)	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).

Secondary Outcome Measures

Name	Time	Method
Change in Total Sleep Time	Day -1-0, Day 89-90	Change in sleep time will be determined by PSG.
Inflammatory Biomarkers C-reactive Protein (CRP)	Baseline
Interleukin 6 (IL-6)	Baseline
Insulin Resistance (IR)	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).