Calorie Restriction With Leucine Supplementation

Study Overview
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Brief Summary
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The purpose of this study is to determine whether consuming additional leucine during calorie restriction induced weight loss has beneficial or harmful effects on multi-organ (liver, muscle, adipose tissue) insulin sensitivity, colonocyte proliferation rates, the gut microbiome, muscle mass and function, and bone mineral density in obese, postmenopausal women.

Official Title
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Calorie Restriction With Leucine Supplementation in Postmenopausal Women

Conditions
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Obesity, Menopause, Osteoporosis, Sarcopenia

Intervention / Treatment
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* Behavioral: Weight loss with normal protein and leucine intake
* Behavioral: Weight loss with protein/leucine supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese with body mass index (BMI) between 30 and 40 kg/m2 Postmenopausal Sedentary (i.e., less than 1.5 hours of exercise per week) Exclusion Criteria: Individuals with diabetes and/or uncontrolled hypertension Individuals with hepatitis B and/or C Individuals who smoke Individuals with an allergy to whey protein

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Weight maintenance<br>Weight maintenance with normal protein and leucine intake | |
| Active Comparator: Weight loss with normal protein intake<br> | Behavioral: Weight loss with normal protein and leucine intake<br>* Goal of 8 to 10% weight loss while consuming the recommended daily allowance of protein (i.e, 0.8 grams of protein per kg body weight per day).<br>|
| Experimental: Weight loss with leucine supplementation<br> | Behavioral: Weight loss with protein/leucine supplementation<br>* Goal of 8 to 10% weight loss while consuming 150% of the recommended daily allowance of protein (i.e., 1.2 grams of protein per kg body weight per day) with the additional protein given in the form of whey protein, which has a high leucine content.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle mass | We will measure total appendicular skeletal muscle mass by using dual-energy X-ray absorptiometry (DXA) and thigh muscle volume by magnetic resonance imaging (MRI) | Baseline and at 10% weight loss in calorie restriction groups and  6 to 7 months in the weight maintenance group | 
| Change in muscle strength | We will evaluate muscle strength by administering maximum one repetition strength and isokinetic strength tests. | Baseline and at 10% weight loss in calorie restriction groups and  6 to 7 months in the weight maintenance group | 
| Change in bone mineral density and bone mineral content | We will evaluate total bone mass and total body and regional bone mineral density by using dual X-ray energy absorptiometry (DXA). | Baseline and at 10% weight loss in calorie restriction groups and  6 to 7 months in the weight maintenance group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skeletal muscle insulin sensitivity | We will evaluate insulin sensitivity using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope labeled tracer infusions | Baseline and at 10% weight loss in calorie restriction groups and  6 to 7 months in the weight maintenance group | 
| Change in bacterial populations found in the stool |  | Baseline and at 10% weight loss in calorie restriction groups and  6 to 7 months in the weight maintenance group | 
| Change in cell proliferation (growth) rates in the colon | We will examine colon cell proliferation rates using stable isotope labelled tracer methods in conjunction with sigmoid colon biopsy samples | Baseline and at 10% weight loss in calorie restriction groups and  6 to 7 months in the weight maintenance group | 
| Determine the acute effect of leucine ingestion on skeletal muscle insulin sensitivity | We will evaluate insulin sensitivity using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope labeled tracer infusions | Prior to starting the weight loss or maintenance intervention | 
| Determine the acute effect of leucine ingestion on muscle protein metabolism | We will assess rates of muscle protein synthesis, breakdown and net protein balance using stable isotope labeled tracer methods during postabsorptive conditions and during insulin infusion with or without leucine ingestion. | Prior to starting the weight loss or maintenance intervention |