TRE: Microbiome, Metabolic Health and Bone

Study Overview
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Brief Summary
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In the Time-Restricted Eating: Microbiome and Bone (TREMBO) study, the primary goal is to determine the effect of time-restricted eating with caloric restriction compared to caloric restriction alone on body weight, the gut microbiota, and bone health in older women who are overweight or obese.

Detailed Description
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Time-restricted eating (TRE) has gained increased attention due to the possibility to induce weight loss and improve cardiometabolic health as a result of the purported alignment of circadian rhythm. However, since TRE is often reported to cause a spontaneous reduction of calories, it is not well understood if these health benefits are due to weight loss, circadian rhythm alignment, or a combination of the two. Furthermore, while weight loss can improve cardiometabolic health, it can also induce bone loss, which is problematic in older women who are at a higher risk of fracture. Interestingly, both bone turnover and the gut microbiota are responsive to diurnal variations, such as meal timing, and alterations in the gut microbiota have been associated with differences in bone health. In rodent models, caloric restriction can alter the gut microbiota composition with further alterations shown due to time-restricted eating. This suggests that time-restricted eating could affect bone health, which may be partially mediated by changes in the gut microbiota. Also, lifestyle patterns affects both the microbiota and bone. This randomized controlled trial will use behavior modification to examine TRE plus caloric restriction (CR) to achieve an evening energy deficit compared to CR alone on body weight, the gut microbiota, and bone health in older women who are overweight or obese.

Official Title
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Time Restricted Eating on the Microbiome Affecting Metabolic Health and Bone in Older Women

Conditions
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Weight Loss, Time Restricted Feeding, Bone Loss

Intervention / Treatment
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* Behavioral: Time Restricted Eating (TRE)
* Behavioral: Calorie Restriction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women (>2 years since last menses) Body mass index (25-45 kg/m2) Agree to be randomly assigned to consume food for ≤ 9 hours/day or ≥12 hours/day Must attend on-site visits (about 10) in New Brunswick, NJ, USA (transportation/reimbursement for travel not included) Exclusion Criteria: Participants with >5% weight loss in the past 6 months or extreme dietary/physical activity habits An inability to follow the experimental intervention or to perform the required specimen collections Antibiotic use in the past 2 months Current diagnosis, or history of cancer in past 3 years History of surgical procedure for weight loss in the past 3 years Current diagnosis or history of bone diseases, type I or II diabetes, gastrointestinal disease, hyperparathyroidism, untreated thyroid disease, significant immune, hepatic, cardiac, or renal disease Uncontrolled hypertension or hyperlipidemia in abnormal ranges Regular use of medications that affect bone metabolism, including bisphosphonates or hormone replacement. A colonoscopy within the past 2 months Alcohol or illicit drug abuse Current smoker or having quit smoking in the past 3 months Shift work Participation in another clinical research trial which may interfere with the results of this study.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 79 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial Enroll 48 to achieve sample size of 40 (20/group)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Time restricted eating and calorie restriction<br>Subjects will be asked to adhere to a calorie-restricted diet and will be counseled by a dietitian for diet and lifestyle behavior education. In addition, they will be asked to only consume calories during a 9-hour window (15:9). | Behavioral: Time Restricted Eating (TRE)<br>* 9-hour eating window<br>Behavioral: Calorie Restriction<br>* daily calorie restriction<br>|
| Active Comparator: Calorie restriction alone<br>Subjects will be asked to adhere to a calorie-restricted diet and will be counseled by a dietitian for diet and lifestyle behavior education. They will be advised to continue to consume foods throughout the day and into the evening. | Behavioral: Calorie Restriction<br>* daily calorie restriction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss | Body weight in kg | change from baseline to an average 6 months | 
| Bone mineral density (BMD - hip) | dual energy x-ray absorptiometry | change from baseline to an average 6 months | 
| Microbiota | stool | change from baseline to an average 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soft tissue (lean and fat mass) | dual energy x-ray absorptiometry | change from baseline to an average 6 months | 
| Areal BMD (lumbar spine, femoral neck, radius, total body) | dual energy x-ray absorptiometry | change from baseline to an average 6 months | 
| Trabecular bone (volumetric BMD, bone volume / total volume, and separation) | peripheral quantitative computed tomography | change from baseline to an average 6 months | 
| Cortical bone (volumetric BMD, thickness, and porosity) and total BMD | peripheral quantitative computed tomography | change from baseline to an average 6 months | 
| Blood pressure (systolic and diastolic) | sphygmomanometer | change from baseline to an average 6 months | 
| Glucose - response to oral glucose tolerance test | fasting and response to glucose solution | change from baseline to an average 6 months | 
| Insulin - response to oral glucose tolerance test | fasting and response to glucose solution | change from baseline to an average 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone mineral density, Microbiome, obesity and overweight, metabolic health, time restricted feeding, energy restriction