Impact of Sleep Restriction in Women

Study Overview
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Brief Summary
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The overall goal of this project is to test the hypothesis that long-term, sustained sleep restriction (SR), in women, will lead to increased cardio-metabolic risk. This will be characterized by increases in visceral adiposity, unhealthy lifestyle behaviors (poor dietary quality and low physical activity) and cardio-metabolic risk factors (blood pressure, glucose intolerance) relative to habitual sleep (HS). The investigators expect these changes to be worse in pre- compared to post-menopausal women.

Detailed Description
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This project is funded by the American Heart Association Go Red for Women Strategically Focused Research Network (SFRN). This SFRN includes two separate projects: Clinical Science Project (PI, St-Onge) and Basic Science Project (PI, Jelic). Women are enrolled in the Clinical Science project and given the option to enter the Basic Science project. Each project (clinical and basic) has its own separate primary and secondary outcomes. For the Clinical Science project, primary outcomes are glucose tolerance and ambulatory and office blood pressure; and secondary outcomes are body composition and circulating inflammatory markers. For the Basic Science project, the primary outcomes are flow mediated dilatation of the brachial artery (FMD) and secondary outcomes are endothelial cell oxidative stress and inflammation. The results of these two projects will be reported in separate and in combined publications. This study will be a randomized, crossover, outpatient sleep restriction (SR) study with 2 phases of 6 weeks each, with a 6 week wash-out period between the phases. Sleep duration in each phase will be the participant's regular bed- and wake times during the habitual sleep (HS) phase and HS minus 1.5 hours in the SR phase. During the HS phase, participants will be asked to follow a fixed bedtime routine based on their screening sleep schedule. During the SR phase, participants will be asked to keep their habitual wake time constant but delay their bedtime to achieve a reduction of 1.5 hours in total sleep time. On the first day of each study phase (baseline), participants will come to the research center in the morning after an overnight,12 hour fast. Participants will have anthropometric measurements taken and will then be taken to the department of Radiology to undergo magnetic resonance imaging (MRI) scanning to assess body composition. Flow-mediated dilatation will be performed in the Cardiovascular Ultrasound Laboratory followed by endothelial cell harvesting (Basic Science project). A sample of cells lining the blood vessel (forearm vein) will be taken to assess endothelial function. Women will undergo an oral glucose tolerance test (Clinical Science project). Blood samples will be taken for hormone measurements (insulin, cortisol). Participants will begin the fixed bedtime routine that night. These baseline measurements will be repeated at endpoint, 6 weeks later. Body weight and waist circumference will be measured weekly and fasting blood samples will be taken at weeks 3 and 4 during adherence check visits. To verify that participants adhere to the sleep protocol, they will be asked to keep a sleep diary and wear an activity monitor 24 hours/day. Participants will wear an actigraph GT3X+ on their wrist, which will serve to track their sleep duration, sleep timing, and physical activity. Two weeks prior to randomization and during the washout period, participants will also wear the actigraph watch and keep a sleep diary to verify sleep duration and sleep-wake schedule. In addition to achieving an average sleep of 7-9 hours/night, by wrist actigraphy, participants will only be enrolled if they achieve 7 hours of sleep for at least 10 of the 14 nights of screening and have <4 nights with <6 hours of sleep. At the time of randomization, a urine pregnancy test and drug screen will be performed. Participants will be asked to abstain from caffeine and alcohol intake for 24 hours prior to the start. Between study phases, if participants have not returned to baseline sleep patterns within the 6 week washout period, an additional 2-4 week washout period will be provided. This washout length will ensure that women are in the same phase of their menstrual cycle at the start of each experimental phase.

Official Title
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Impact of Sleep Restriction on Cardiometabolic Risk Factors in Pre vs Postmenopausal Women

Conditions
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Sleep, Cardiovascular Disease, Obesity

Intervention / Treatment
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* Other: Sleep Restriction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-75 years old All racial/ethnic groups Body mass index 18.5-34.9 kg/m2 Sleep 7-9 h in bed/night with no daytime nap Normal scores on: Pittsburgh Quality of Sleep Questionnaire Epworth Sleepiness Scale, Berlin Questionnaire, Sleep Disorders Inventory Questionnaire, Beck Depression Inventory, Composite Scale of Morningness/Eveningness, Three Factor Eating Questionnaire Exclusion Criteria: Smokers (any cigarettes or ex-smoker <3 years) Neurological, medical or psychiatric disorder Diabetics Regular use of any medication or supplement Eating and/or sleep disorders Contraindications for MRI scanning Travel across time zones within 4 wk History of drug and alcohol abuse Shift worker (or rotating shift worker) Caffeine intake >300 mg/d Oral contraceptive use or hormone replacement therapy Heavy equipment operators Commercial long-distance drivers.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Habitual Sleep (HS)<br>During the HS phase, participants will be asked to follow a fixed bedtime routine based on their screening sleep schedule. | |
| Experimental: Sleep Restriction (SR)<br>During the SR phase, participants will be asked to keep their habitual wake time constant but delay their bedtime to achieve a reduction of 1.5 h in total sleep time. A delay in bedtimes was chosen rather than advancing wakeup time because it most closely reflects differences in sleep timing behavior between short and normal sleepers. | Other: Sleep Restriction<br>* Mild sleep restriction (-1.5 h/night) over a period of 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose tolerance | Oral glucose tolerance test | baseline to 6 weeks | 
| Change in blood pressure | 24-hour ambulatory blood pressure; weekly office blood pressure | baseline to 6 weeks | 
| Flow-mediated dilatation | Endpoint FMD | baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Adiposity | Body composition measured by magnetic resonance imaging | baseline to 6 weeks | 
| Change in physical activity levels | Time in various behaviors: sedentary, light, moderate, moderate-to-vigorous physical activity | baseline to 6 weeks | 
| C-reactive protein | Inflammatory markers | Weeks 0, 3, 4, and 6 | 
| Interleukin-6 | Inflammatory markers | Weeks 0, 3, 4, and 6 | 
| Tumor necrosis factor | Inflammatory markers | Weeks 0, 3, 4, and 6 | 
| T cell reactivity to viral loads | Immune markers | Weeks 0 and 6 | 
| Cholesterol | Total, low-density, and high-density lipoprotein | Weeks 0 and 6 | 
| Triglycerides | Lipidemia | Weeks 0 and 6 | 
| Endothelial cell oxidative stress | redox sensitive fluorogenic probe fluorescence intensity | Baseline to 6 weeks | 
| Endothelial inflammation | NF-κB nuclear fluorescence area | baseline to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Metabolic Disorders