Exogenous Melatonin in Postmenopausal Women With Insomnia

Study Overview
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Brief Summary
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The aim of the study is to assess the effect of exogenous melatonin, 2 mg SR, 60 minutes before bedtime for 15 days, on the sleep and circadian rhythms of postmenopausal women with insomnia in a randomized crossover placebo-controlled study.

Detailed Description
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Eligible participants will be contacted by the research team to provide informed consent for the study. Once the screening phase is completed, they will be ready to start the study consisting of: A) a  2-week ambulatory phase at home with melatonin or placebo treatment; B) a 2-week wash-out period; C) same as A with the opposite treatment; Part A: The research project will start with a 16-day ambulatory data-collection period during which participants will receive either melatonin or a placebo. They will take 2 mg of exogenous melatonin in a slow release formulation (or placebo), 60 mins prior to bedtime for 15 days. Participants will be instructed to go to bed at a regular time and stay in darkness for 8 consecutive hours each night, trying to sleep. Part B: Throughout this period, all participants will stop taking their melatonin/placebo pills. After at least 2 weeks, they will prepare to participate to the other study condition. Parts C: Repetition of Ambulatory phase 1 (Part A) except that participants who received the active treatment will now receive placebo and vice versa.

Official Title
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Sleep and Circadian Rhythms in Men and Women - Protocol 4

Conditions
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Insomnia

Intervention / Treatment
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* Drug: Melatonin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Insomniac women will meet the diagnostic criteria for persistent insomnia as described in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). They will report subjective sleep onset and/or maintenance difficulties associated with impaired daytime functioning at least 3 times a week, for at least 3 months. Sleep disturbances will be coincident with the onset of the menopausal transition. Postmenopausal women will have amenorrhea for at least 12 months. Participants will be drug-free at the time of study, and will have a history of only moderate or no use of coffee (≤3 cups/day), tobacco (≤ 10 cigarettes/day), alcohol (≤ 15 drinks/week), or other compounds. Exclusion Criteria: Evidence of psychopathology on the Structured Clinical Interview for DSM-5, the Seasonal Pattern Assessment Questionnaire, the Beck Depression Inventory, and the Spielberger State Trait Anxiety Inventory. A history of prior gynecological pathology or medical condition that can affect the study results, including bilateral oophorectomy or endocrinopathy, and will not have used investigational drugs within 4 weeks of the study. A history of night work or transmeridian travel (across >2 time zones) in the 2 months prior to the study. Evidence of sleep apnea (apnea/hypopnea index > 15 per hour of sleep) or restless legs, or periodic limb movements during sleep (number of PLMs >15 per hour of sleep).

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Crossover Assignment
Interventional Model Description: Randomized crossover placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br>2 mg oral tablet, melatonin slow release formulation, 1x 60 min before bedtime for 15 days | Drug: Melatonin<br>* 2 Mg Oral Tablet, slow release<br>|
| Placebo Comparator: Placebo<br>2 mg oral tablet, 1x 60 min before bedtime for 15 days | Drug: Placebo<br>* placebo pill identical to the treatment pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sleep duration | Sleep recorded with a portable device | Change from baseline sleep duration at treatment day 15 | 
| Change in wake after sleep onset | Sleep recorded with a portable device | Change from baseline sleep duration at treatment day 15 | 
| Change in sleep efficiency | Sleep recorded with a portable device | Change from baseline sleep duration at treatment day 15 | 
| Urinary 6-sulfatoxy-melatonin levels | Urinary samples | During sleep periods during the last 3 days of each treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) | A self-rated 19-item questionnaire, each of which has a range of 0 (no difficulty) to 3 (severe difficulty) points.These 19 items are combined to form 7 component scores reflecting different aspects of sleep quality. The 7 component scores are then added to yield one global score, with a range of 0-21 points, 0 indicating no difficulty and 21 indicating severe difficulties in all area. | Change between treatment conditions in PSQI score at treatment day 15 | 
| Nocturnal skin temperature | Skin measured around the nocturnal sleep periods | Change between treatment conditions at bedtime at treatment days 14-15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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menopause, aging, melatonin, circadian rhythms, sleep, alertness