Effect of Time-Restricted Feeding on Fat Loss and Cardiometabolic Risk Factors in Overweight Adults

Study Overview
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Brief Summary
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Time-restricted feeding (TRF) is a novel type of intermittent fasting that involves eating within a daily period of 10 hours or less, followed by fasting for at least 14 hours daily. Several studies in rodents report that TRF reduces body weight, improves blood sugar control, and reduces the risk of cardiovascular disease-even when food intake is matched to the control group or no weight loss occurs. Preliminary evidence suggests that TRF may also increase weight loss, fat loss, and reduce the risk of diabetes and cardiovascular disease in humans. This study will test whether TRF enhances fat loss and increases weight loss in adults with obesity, relative to conventional dieting alone. In addition, this study will determine whether TRF reduces risk factors for type 2 diabetes and cardiovascular disease and will measure the feasibility and acceptability of TRF. In conjunction with the parent study described above, four ancillary studies will be conducted: Effect of weight loss on nitrogen metabolism and bacteria in the mouth. The primary endpoints for this ancillary study are plasma and salivary nitrate and nitrite, and the secondary endpoints are salivary nitrate reductase activity and salivary bacterial abundance. Effect of weight loss on several biomarkers related to kidney stones. The primary endpoint for this ancillary study is urinary oxalate, and the secondary endpoints are urinary citrate, chloride, sodium, potassium, calcium, phosphorus, uric acid, and creatinine. Effect of meal timing on blood pressure regulation and kidney function. The primary endpoints of this ancillary study include urinary aldosterone excretion, sodium, potassium, and endothelin, whereas the secondary endpoints include nitric oxide and albumin. Additional exploratory endpoints include renal injury markers (KIM-1, nephrin, and urine albumin-to-creatinine ratio), measures of reactive oxidative stress (e.g., hydrogen peroxide and TBARs), and urinary exosomes. Urine will be analyzed in 12-hour bins to determine how meal timing affects differentially affects these endpoints during the daytime and nighttime. The effects of weight loss on these endpoints may also be considered. Validation of a meal timing questionnaire to assess the distribution of food intake throughout the day.

Official Title
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Effect of Time-Restricted Feeding on Fat Loss and Cardiometabolic Risk Factors in Overweight Adults

Conditions
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Obesity

Intervention / Treatment
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* Behavioral: Early Time-Restricted Feeding
* Behavioral: Control Schedule
* Behavioral: Structured Weight Loss Program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are a new patient at the UAB Weight Loss Medicine Clinic Aged 25-75 years old BMI between 30-60 kg/m2 (inclusive) Weigh less than 450 lbs Wake up regularly between 4-9 am on most days. Exclusion Criteria: Diagnosed with diabetes, have an HbA1c of ≥6.5%, or are on diabetes medication On weight loss medication Addition of or withdrawal from a chronic medication within the past 10 weeks Clinically significant laboratory abnormality (e.g., abnormal hemoglobin levels) Significant gastrointestinal disease, major gastrointestinal surgery, or gallstones Significant cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that might compromise the participant's safety or data validity Evidence of cancer (other than non-melanoma skin cancer) within the last 5 years Unstable psychiatric, sleep, or circadian conditions (common conditions such as sleep apnea and depression are acceptable as long as they are stabilized and not rapidly worsening) Lost or gained more than 5 lbs of weight in the past month Currently perform overnight shift work more than once per week on average Regularly eat within a less than 10-hour period each day Regularly eat dinner before 6 pm Traveled more than two time zones away in the two months prior to enrolling in the trial Will travel more than one time zone away during the study Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Time-Restricted Feeding<br> | Behavioral: Early Time-Restricted Feeding<br>* Eat all meals between 7 am - 3 pm for an average of ≥6 days per week.<br>* Other names: eTRF;Behavioral: Structured Weight Loss Program<br>* A structured weight loss program with physical activity recommendations and dietary counseling.<br>|
| Active Comparator: Control Schedule<br> | Behavioral: Control Schedule<br>* Eat all meals over a 12-hour or longer period for an average of ≥6 days per week.<br>Behavioral: Structured Weight Loss Program<br>* A structured weight loss program with physical activity recommendations and dietary counseling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat loss and lean mass retention | Percent of weight lost as fat, as measured by dual-energy X-ray absorptiometry (DXA). Lean mass retention will be quantified as 100% minus percent of weight lost as fat (i.e., is measured in the same units). | 14 weeks | 
| Weight loss | Change in body weight (kg), as measured by scale weight | 14 weeks | 
| Absolute changes in body composition | Changes in total fat mass, lean mass, bone mass, and regional values (kg), as measured by DXA. (This will be secondary to the assessment of fat loss and lean mass retention as specified above.) | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting glucose | Fasting glucose (mg/dl) | 14 weeks | 
| Fasting insulin | Fasting insulin (IU/L) | 14 weeks | 
| HbA1c | HbA1c (%) | 14 weeks | 
| Lipids | Total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl) | 14 weeks | 
| Blood pressure | Systolic and diastolic blood pressure (mm Hg) | 14 weeks | 
| Heart rate | Heart rate in beats per minute | 14 weeks | 
| Waist circumference | Waist circumference (cm) | 14 weeks |