Effects of Red Grape Cells (RGC) Powder on Glycemic and Lipid Control in Patients With Type 2 Diabetes ¬ A Double-blind, Randomized, Placebo Controlled Study

Effects of Red Grape Cells (RGC) Powder in Type 2 Diabetics

Sponsors

Lead sponsor: Tel Aviv University

Collaborator: Wolfson Medical Center

Source Tel Aviv University
Brief Summary

The aim of this study is to examine whether the chronic administration during 12 weeks of polyphenols contained in Red Grape Cells (RGC) powder has an effect on mRNA expression of SIRT1 and Clock Genes, on circulating levels of HbA1c, lipids, blood pressure and on postprandial response of glucose, lipids, insulin, C-peptide and GLP-1 in patients with type 2 diabetes .

Detailed Description

There is a growing body of evidence demonstrating that polyphenols and specially the most investigated Resveratrol contained in the Red Grape Cells (RGC) exert beneficial effects on several markers of metabolic syndrome i.e. antioxidant, anti-inflammatory, anti-atherosclerotic, vasodilator and antihypertensive activity.

Many of this beneficial metabolic effects of polyphenols, occurs via activation of sirtuin-1 or silent information regulator-1 gene (SIRT1). This gene is expressed in adipose tissue, muscle, endothelium, peripheral blood cells, etc where it plays a pivotal role in the regulation of Circadian Clock Genes (CCG) involved in glucose lipid metabolism, endothelial function, etc .

By activation of SIRT1 and CCG the polyphenols, may influence the circadian secretion of adiponectin, insulin, asymmetric dimethylarginine (ADMA) and other hormones that influence insulin sensitivity, muscular glucose uptake, NO synthesis, nocturnal hepatic glucose production, lipolisis and endothelial function It was shown in several studies in animals and in clinical studies in subjects with metabolic syndrome that SIRT1 expression and its regulation of the CCG, improves insulin sensitivity in skeletal muscle, preventing weight gain; improves pancreatic beta-cell function enhancing insulin secretion and glucose tolerance. It was associated with increased lipolisis in white adipose tissue, decreased glycolysis, increased fatty acid oxidation in skeletal muscle and with increase Nitric Oxide in the endothelium.

Given that polyphenols directly on the clock genes or by enhancing SIRT1 expression appears to counter some of the effects of a high-fat diet, obesity and metabolic syndrome, by protecting against insulin resistance, hyperglycemia, and dyslipidemia and endothelial dysfunction.

It rise the possibility that the polyphenols contained in Red Grape Cells (RGC) by activation SIRT1 may also exert beneficial effects in subjects affected by type 2 diabetes

Overall Status Completed
Start Date September 2013
Completion Date November 2017
Primary Completion Date February 2014
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Fasting and postprandial Clock Genes expression in peripheral blood cells (PBC) Fasting and every hour after meal challenge in two occasions : at baseline (day 1) and after 12 weeks of of supplementation with RGC or Placebo .
Secondary Outcome
Measure Time Frame
Fasting HbA1c Fasting blood levels will be taken at baseline and after 12 weeks of supplementation with RGC or placebo
Enrollment 40
Condition
Intervention

Intervention type: Dietary Supplement

Intervention name: Red Grape Cells (RGC)

Description: Red Grape Cells (RGC) 1000 mg powder once daily by mouth for three month

Arm group label: Red Grape Cells (RGC)

Other name: RGC

Intervention type: Dietary Supplement

Intervention name: Placebo (for Red Grape Cells (RGC))

Description: Placebo (for Red Grape Cells (RGC)) powder manufactured to mimic Red Grape Cells (RGC) 1000 mg powder

Arm group label: Placebo (for Red Grape Cells (RGC))

Other name: RGC Placebo

Eligibility

Criteria:

Inclusion Criteria:

1. Type 2 diabetes patients

2. HbA1C > 7 %

3. Duration of diabetes: 0.5 to 20 years

4. Subjects ≥ 30 and ≤70 years of age

5. BMI: 22 to 35 kg/m2

6. Fasting Triglyceride serum level ≥ 150 mg/dl

7. All oral antidiabetic treatments will be allowed, with the exception of thiazolidinediones (glitazones).i.e. pioglitazone (Actos) or rosiglitazone (Avandia). Insulin and no GLP-1 analogs will not be allowed.

8. Normal liver and kidney function

9. Normal thyroid function

10. Acceptable health beside diabetes based on interview, medical history, physical examination, and laboratory tests

11. Willingness to avoid the use of over-the-counter medications, herbs, or supplements throughout the entire study.

12. Willingness to avoid ingestion of any foods containing peanuts, bilberries, blueberries, cranberries, strawberries, raspberries, grapes, grape juice, cocoa powder, dark chocolate, and red wine throughout the entire study

13. Stable physical activity pattern during the three months immediately preceding study

14. Usually wakes up between 06:00 and 07:00 and goes to sleep between 22:00 and 24:00.

15. No shift work within 5 years of the study

16. Did not cross time zones within 1 month of the study

17. Read and understood the informed consent form and signed it voluntarily

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Exclusion Criteria:

1. Type 1 diabetes

2. Clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, malignant disease

3. Abnormal liver function tests defined as an increase by a factor of at least 2 above the upper normal limit of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)

4. Pregnancy or lactation

5. Illicit drug abuse or alcoholism

6. Treatment with thiazolidinediones (glitazones).i.e. pioglitazone (Actos) or rosiglitazone (Avandia).

7. Insulin and or GLP-1 analogs will not be allowed.

8. Anti hyperlipidemic treatment with fibrates. Statins will be allowed

9. Subjects taking anoretic drugs during the month immediately prior to study

10. Subjects on steroid treatment

11. Those with major illnesses, liver, heart, kidney, lung, infectious, neurological, psychiatric, immunological or neoplastic diseases,

12. Those with eating disorders

13. Known hypersensitivity to grapes, soy and/or casein

14. Subjects after bariatric surgery, will be excluded

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Gender: All

Minimum age: 30 Years

Maximum age: 70 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Daniela Jakubowicz, MD Principal Investigator Diabetes Unit E. Wolfson Medical Center. Tel Aviv University
Location
facility
Daniela Jakubowicz MD
Location Countries

Israel

Verification Date

August 2018

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Tel Aviv University

Investigator full name: Daniela Jakubowicz

Investigator title: Prof. Daniela Jakubowicz MD

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Red Grape Cells (RGC)

Arm group type: Experimental

Description: Red Grape Cells (RGC) 1000 mg powder once daily by mouth for three month

Arm group label: Placebo (for Red Grape Cells (RGC))

Arm group type: Placebo Comparator

Description: Placebo (for Red Grape Cells (RGC)) similar powder to mimic 1000 mg of Red Grape Cells (RGC), once daily by mouth for three month

Acronym RGC-T2D
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov