Effects of Red Grape Cells (RGC) Powder in Type 2 Diabetics (RGC-T2D)

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

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 .

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Dietary supplement: Red Grape Cells (RGC); Dietary supplement: Placebo (for Red Grape Cells (RGC))

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

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv
    • Holon,, Tel Aviv, Israel, 58100
      • Daniela Jakubowicz MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Red Grape Cells (RGC); Red Grape Cells (RGC) 1000 mg powder once daily by mouth for three month	Dietary supplement: Red Grape Cells (RGC); Red Grape Cells (RGC) 1000 mg powder once daily by mouth for three month; Other Names: RGC
Placebo Comparator: Placebo (for Red Grape Cells (RGC)); Placebo (for Red Grape Cells (RGC)) similar powder to mimic 1000 mg of Red Grape Cells (RGC), once daily by mouth for three month	Dietary supplement: Placebo (for Red Grape Cells (RGC)); Placebo (for Red Grape Cells (RGC)) powder manufactured to mimic Red Grape Cells (RGC) 1000 mg powder; Other Names: RGC Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting and postprandial Clock Genes expression in peripheral blood cells (PBC)	In all 40 subjects the effects of 12 weeks supplementation with RGC or placebo will be assessed .The clock gene expression will be measured in peripheral blood cells (PBC), at baseline (Day 1) and again after 12 weeks of supplementation The blood samples will be taken for Clock Genes expression at fasting and after meal challenge every hour until 4 hours	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 Measures

Outcome Measure	Measure Description	Time Frame
Fasting HbA1c	In all 40 subjects, fasting blood levels for HbA1c, will be measured at baseline and after 12 weeks of supplementation treatment with RGC n=20 or placebo n=20	Fasting blood levels will be taken at baseline and after 12 weeks of supplementation with RGC or placebo

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
fasting and postprandial glucose, Insulin, GLP-1, asymmetric dimethylarginine (ADMA),and lipid plasma levels	In all 40 subjects the effects of RGC ingestion or placebo will be evaluated in at baseline and after 12 weeks of supplementation with RGC or placebo. The blood samples will be taken at fasting and every hour up to 4 hours after meal challenge for quantification of Glucose, Insulin, glucagon-like peptide-1 (GLP-1), ADMA and for lipid plasma levels.	The samples will be taken at fasting and every hours until 4 hours after meal challenge, in to occasions at baseline and after 12 week of supplementation with RGC or Placebo

Collaborators and Investigators

• Sponsor: Tel Aviv University
• Collaborators: Wolfson Medical Center
• Investigators: Principal Investigator: Daniela Jakubowicz, MD, Diabetes Unit E. Wolfson Medical Center. Tel Aviv University

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: September 1, 2013
• First Submitted That Met QC Criteria: September 4, 2013
• First Posted (Estimate): September 10, 2013

Study Record Updates

• Last Update Posted (Actual): August 28, 2018
• Last Update Submitted That Met QC Criteria: August 26, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Red Grape Cells powder (RGC); Placebo (PLA)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 0107-13-WOMC