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

Study Overview
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Brief Summary
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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.

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

Conditions
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Insomnia

Intervention / Treatment
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* Drug: ramelteon
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ramelteon<br>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. | Drug: ramelteon<br> <br> * Other names: Rozerem;|
| Placebo Comparator: placebo<br>15 subjects will be randomized to receive the placebo | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | 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. | Day 89-90 | 
| Mean Latency to Persistent Sleep (LPS) Via Polysomnography | Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured. | Day 89-90 | 
| 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) | 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). | baseline | 
| Sleep Onset Latency (SOL) as Measured by Pittsburgh Sleep Qualtiy Index (PSQI) | 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). | day 89 - 90 | 
| Mean Latency to Persistent Sleep (LPS) Via Polysomnography | Elapsed time from the beginning of the Polysomnography recording to the onset of the first 20 minutes of continuous sleep was measured. | Baseline | 
| Sleep Onset Latency (SOL) as Measured by Self Report (Sleep Diary) | The average of a week of sleep onset latency data from the sleep diary filled out in the morning by the participating subjects. | Baseline | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insomnia