Resveratrol-Leucine Metabolite Synergy in Pre-diabetes

Study Overview
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Brief Summary
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The study will evaluate the effects of resveratrol/leucine and resveratrol/HMB for their ability to control glucose levels in persons without diabetes but with impaired fasting glucose. Secondary assessments will examine the effect of these nutritional supplements versus placebo on inflammation, fasting lipids, HbA1C, and fructosamine, longer term metabolic markers of risk in diabetes.

Detailed Description
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This will be a 28-day randomized controlled trial of the effects of a nutraceutical preparation on glycemic control in non-diabetic individuals with impaired glucose tolerance (IGT). IGT will be defined by American Diabetes Association criteria, as outlined in the list of inclusion and exclusion criteria (copy attached). There will be two active treatment arms and a placebo arm (3 arms total, n=12 completed subjects per arm). Following screening for inclusion/exclusion criteria and obtaining informed consent, subjects will be enrolled in the study and provided instructions to maintain their usual dietary pattern and physical activity level. If recent physical examination and medical history are not available; H&P will be conducted and recorded for each enrolled subject. Subjects will be instructed to follow a 12-hour fast starting on day -1, and on the morning of day 0 fasting blood is drawn for analyses indicated below and the supplements are distributed. Supplements are distributed using a blinding protocol and a variable, known pill allotment in order to assess compliance via standard pill counts. Pill bottles and all unused supplements are returned at seven day intervals, with new supplies being distributed at that time. Fasting blood samples are obtained on days 0, 7, 14 and 28. Samples from each day are analyzed for glucose and insulin. Samples from days 0, 14 and 28 are also analyzed for fructosamine, C-peptide, glucagon and F2-isoprostanes. A75 g oral glucose tolerance test administered on days 0 and 28.

Official Title
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Resveratrol-Leucine Metabolite Synergy in Pre-diabetes

Conditions
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Impaired Glucose Tolerance

Intervention / Treatment
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* Dietary Supplement: Resveratrol
* Dietary Supplement: resveratrol /HMB
* Other: Placebo treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Impaired fasting glucose as defined by American Diabetes Association criteria: fasting plasma glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL) Body mass index (BMI) 25-34.9 Age 18 and above• Weight stable: no more than 1 kg weight gain or loss during past 12 weeks Exclusion Criteria: Fasting glucose >126 or <99 mg/dL BMI < 25 or >35 Current/previous diagnosis of diabetes History of eating disorder or presence of active gastrointestinal disorders such as malabsorption syndromes Pregnancy or lactation Anemia, defined as hemoglobin level less than 10g/dl. Use of obesity pharmacotherapeutic agents within the last 6 months Use of over-the-counter anti-obesity agents (e.g. those containing phenylpropylamine , ephedrine and/or caffeine) within the last 3 months Chronic use of anti-inflammatory agents within the last four weeks Use of antioxidant supplements within the last four weeks including selenium, vitamin E, vitamin C and/or carotenoids Use of supplements containing any of the study compounds within the past four weeks Recent (current or past 12 weeks) use of any psychotropic medication Recent (past four weeks) initiation of or change in an exercise program Recent (past twelve weeks) initiation of hormone replacement therapy or change in HRT regimen Recent (past twelve weeks) initiation of hormonal birth control or change in hormonal birth control regimen Recent (past 12-weeks) history of tobacco use Any Condition that the P.I. considers adverse to the participant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dietary Supplement/insulin sensitivity<br>The first study supplement contains resveratrol that may improve insulin sensitivity and Leucine.Resveratrol 50mg with leucine 1.11 g. - one tablet taken twice a day by mouth | Dietary Supplement: Resveratrol<br>* A blend of low dose resveratrol and either leucine or HMB will be useful nutraceutical strategies for the control of elevated blood glucose in non-diabetic individuals with elevated fasting glucose. The proposed project is designed to evaluate this hypothesis by comparing the effects of resveratrol (50 mg)/leucine (1.11 g) administered twice daily (bid).<br>|
| Placebo Comparator: Sugar Pill<br>Neutral treatment Placebo - one tablet taken twice a day by mouth | Other: Placebo treatment<br>* Placebo - one tablet taken twice a day by mouth<br>|
| Active Comparator: Dietary Supplement 2<br>2nd study supplement contains resveratrol and HMB which may stimulate protein building. | Dietary Supplement: resveratrol /HMB<br>* resveratrol (50 mg)/HMB (500 mg) twice daily (bid) with placebo on fasting blood glucose, glucose tolerance, insulin, C-peptide, glucagon, fructosamine and F2-isoprostanes in non-diabetic subjects with elevated fasting blood glucose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Control | We will evaluate the effects of resveratrol/leucine and resveratrol/HMB for their ability to control glucose levels in persons without diabetes but with impaired fasting glucose | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic Markers | Secondary assessments will examine the effect of these nutritional supplements versus placebo on inflammation, fasting lipids, HbA1C, and fructosamine, longer term metabolic markers of risk in diabetes | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Impaired glucose tolerance, pre-diabetes,glycemic control,, supplements