Resveratrol-Leucine Metabolite Synergy in Pre-diabetes

Impaired Glucose Tolerance Clinical Trial

Official title:

Resveratrol-Leucine Metabolite Synergy in Pre-diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01593605
• Other study ID #: KNIS-NCI
• Status: Completed
• Phase: N/A
• First received: May 2, 2012
• Last updated: September 18, 2013
• Start date: February 2012
• Est. completion date: June 2013

Study information

• Verified date: September 2013
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glucose Intolerance
• Impaired Glucose Tolerance
• Prediabetic State

Intervention

Dietary Supplement:
• Resveratrol
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).
• resveratrol /HMB
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.

Other:
• Placebo treatment
Placebo - one tablet taken twice a day by mouth

Locations

Country	Name	City	State
United States	Facility: Vanderbilt University	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	Nutraceutical Discoveries, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (8)

Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. Epub 2006 May 26. Review. — View Citation

Blum CA, Ellis JL, Loh C, Ng PY, Perni RB, Stein RL. SIRT1 modulation as a novel approach to the treatment of diseases of aging. J Med Chem. 2011 Jan 27;54(2):417-32. doi: 10.1021/jm100861p. Epub 2010 Nov 16. Review. — View Citation

Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol. 2005 Apr;6(4):298-305. Review. — View Citation

Sun X, Zemel MB. Leucine and calcium regulate fat metabolism and energy partitioning in murine adipocytes and muscle cells. Lipids. 2007 Apr;42(4):297-305. Epub 2007 Feb 20. — View Citation

Verdin E, Hirschey MD, Finley LW, Haigis MC. Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem Sci. 2010 Dec;35(12):669-75. doi: 10.1016/j.tibs.2010.07.003. Epub 2010 Sep 20. Review. — View Citation

Zemel MB, Sun X. Calcitriol and energy metabolism. Nutr Rev. 2008 Oct;66(10 Suppl 2):S139-46. doi: 10.1111/j.1753-4887.2008.00099.x. Review. — View Citation

Zemel MB. Calcium and dairy modulation of obesity risk. Obes Res. 2005 Jan;13(1):192-3. — View Citation

Zemel MB. Role of calcium and dairy products in energy partitioning and weight management. Am J Clin Nutr. 2004 May;79(5):907S-912S. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No