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Effects of Resveratrol in Patients With Type 2 Diabetes (RED)

Primary Purpose

Type 2 Diabetes

Status

Completed

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

Trans-resveratrol extract from Polygonum Cuspidatum

Placebo

About this trial

This is an interventional basic science trial for Type 2 Diabetes focused on measuring Resveratrol, SIRT1, AMPK

Eligibility Criteria

40 Years - 69 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Ability to give informed consent
Chinese Male
Age 40 to 69 yrs old
For subjects with type 2 diabetes mellitus
- Diagnosis of type 2 diabetes mellitus based on MOH criteria and,
- HbA1c >6.5 during screening

Exclusion Criteria:

Willing to abstain from ingesting large quantities of resveratrol-containing foods (eg. red wine, nuts) Cancer diagnosis that is currently under treatment, is clinically detectable, or that has been treated within the past 5 years Terminal disease or on palliative care Current excessive alcohol intake (>21 units per week for men; 14 units per week for women) On maximal doses of 3 or > oral hypoglycaemic agents On insulin therapy or known type 1 diabetes mellitus Past history of documented or suspected hypoglycemia within last 3 months Past history of recurrent hypoglycemia Past history of serious hypoglycemia as defined by documented hypoglycemia requiring hospital admission Past history of hyperglycemic emergencies within last 6 months Past or current history of hemorrhagic strokes On anti-platelet agents, non-steroidal anti-inflammatory drugs (NSAIDs), anti-coagulation therapy or omega-3 fatty acids History of unexplained bleeding disorders History of any grape allergy History of allergy to local anaesthetic History of surgery with surgery with clips, staples or stents Presence of cardiac pacemaker or metallic foreign body in any part of the body On alternative or traditional medications Treated with another investigational drug within last 6 months Poorly controlled hypertension (SBP >/= 160 or DBP >/= 100) within last one month ALT and/or AST > 1.5 times above upper limit of normal within last 6 months GFR < 50 ml/min/1.73m2 (MDRD equation) within last 6 months

Sites / Locations

Alexandra Health, Khoo Teck Puat Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Resveratrol

Placebo

Arm Description

Trans-resveratrol extract from Polygonum Cuspidatum (Mega Resveratrol, Danbury, USA) was used in the trial.Following the run-in period, subjects who were tolerant of the placebo would proceed to the treatment period. Subjects were given a starting dose of 500 mg daily of either resveratrol.The dose was increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia. Subjects were instructed to abstain from foods with high resveratrol content during the entire duration of the trial.

All subjects underwent a 2-week run-in period during which placebo was administered. The placebo was manufactured so that it was not distinguishable by color, form, or taste from the active drug. Following the run-in period, subjects who were tolerant of the placebo would proceed to the treatment period. Subjects were given a starting dose of 500 mg daily of matching placebo and instructed to abstain from foods with high resveratrol content during the entire duration of the trial. The dose was increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.

Outcomes

Primary Outcome Measures

Skeletal muscle sirtuin 1 (SIRT1) expression

Secondary Outcome Measures

Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression

Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression

Skeletal muscle glucose transporter type 4 (GLUT 4) expression

Glycated hemoglobin (HbA1c)

Body weight

Insulin sensitivity

Lipid profile

Energy expenditure

Physical activity level

Abdominal adipose tissue distribution

Skeletal muscle fibre type composition

Renal function

Serum creatinine

Liver function

Transaminases

Full Information

NCT ID

NCT01677611

First Posted

August 30, 2012

Last Updated

August 31, 2012

Sponsor

Khoo Teck Puat Hospital

Collaborators

National Medical Research Council (NMRC), Singapore

1. Study Identification

Unique Protocol Identification Number

NCT01677611

Brief Title

Effects of Resveratrol in Patients With Type 2 Diabetes

Acronym

RED

Official Title

Effects of Resveratrol in Patients With Type 2 Diabetes: The RED Trial

Study Type

Interventional

2. Study Status

Record Verification Date

August 2012

Overall Recruitment Status

Completed

Study Start Date

December 2008 (undefined)

Primary Completion Date

September 2010 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Khoo Teck Puat Hospital

Collaborators

National Medical Research Council (NMRC), Singapore

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Animal studies indicate that resveratrol, a phytoalexin enriched in the skin of red grapes and a constituent of red wine, is associated with longevity likely through the increased production of a protein, SIRT1. The trial is a proof-of-concept study primarily designed to examine for the first time in humans, the effect of 12 weeks of oral resveratrol on skeletal muscle SIRT1 expression in 10 patients with T2DM in a randomized, placebo-controlled, double-blind fashion. Secondary outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure, physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels and insulin sensitivity.

Detailed Description

Eligible criteria include Chinese males, aged between 40 and 69 years old, with T2DM with a HbA1c of 7.1 to 12% and who have been on a stable oral hypoglycemic regimen for the past 3 months. Subjects who were insulin-dependent, with renal or liver impairment or who were terminally ill were excluded.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes

Keywords

Resveratrol, SIRT1, AMPK

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Resveratrol

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Trans-resveratrol extract from Polygonum Cuspidatum

Other Intervention Name(s)

Mega Resveratrol, Danbury, USA

Intervention Description

Starting dose of 500 mg daily of either resveratrol to be administered on Day 1 and increased by 500 mg per day every 3 days to a maximum dose of 3 g per day in three divided doses if there was no hypoglycemia.

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Skeletal muscle sirtuin 1 (SIRT1) expression

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression

Time Frame

3 months

Title

Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression

Time Frame

3 months

Title

Skeletal muscle glucose transporter type 4 (GLUT 4) expression

Time Frame

3 months

Title

Glycated hemoglobin (HbA1c)

Time Frame

3 months

Title

Body weight

Time Frame

3 months

Title

Insulin sensitivity

Time Frame

3 months

Title

Lipid profile

Time Frame

3 months

Title

Energy expenditure

Time Frame

3 months

Title

Physical activity level

Time Frame

3 months

Title

Abdominal adipose tissue distribution

Time Frame

3 months

Title

Skeletal muscle fibre type composition

Time Frame

3 months

Title

Renal function

Description

Serum creatinine

Time Frame

3 months

Title

Liver function

Description

Transaminases

Time Frame

3 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to give informed consent Chinese Male Age 40 to 69 yrs old For subjects with type 2 diabetes mellitus Diagnosis of type 2 diabetes mellitus based on MOH criteria and, HbA1c >6.5 during screening Exclusion Criteria: Willing to abstain from ingesting large quantities of resveratrol-containing foods (eg. red wine, nuts) Cancer diagnosis that is currently under treatment, is clinically detectable, or that has been treated within the past 5 years Terminal disease or on palliative care Current excessive alcohol intake (>21 units per week for men; 14 units per week for women) On maximal doses of 3 or > oral hypoglycaemic agents On insulin therapy or known type 1 diabetes mellitus Past history of documented or suspected hypoglycemia within last 3 months Past history of recurrent hypoglycemia Past history of serious hypoglycemia as defined by documented hypoglycemia requiring hospital admission Past history of hyperglycemic emergencies within last 6 months Past or current history of hemorrhagic strokes On anti-platelet agents, non-steroidal anti-inflammatory drugs (NSAIDs), anti-coagulation therapy or omega-3 fatty acids History of unexplained bleeding disorders History of any grape allergy History of allergy to local anaesthetic History of surgery with surgery with clips, staples or stents Presence of cardiac pacemaker or metallic foreign body in any part of the body On alternative or traditional medications Treated with another investigational drug within last 6 months Poorly controlled hypertension (SBP >/= 160 or DBP >/= 100) within last one month ALT and/or AST > 1.5 times above upper limit of normal within last 6 months GFR < 50 ml/min/1.73m2 (MDRD equation) within last 6 months

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kian Peng Goh, FRCP

Organizational Affiliation

Alexandra Health, Khoo Teck Puat Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Alexandra Health, Khoo Teck Puat Hospital

City

Singapore

ZIP/Postal Code

768828

Country

Singapore

12. IPD Sharing Statement

Citations:

PubMed Identifier

17086191

Citation

Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. doi: 10.1038/nature05354. Epub 2006 Nov 1.

Results Reference

background

PubMed Identifier

17112576

Citation

Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-22. doi: 10.1016/j.cell.2006.11.013. Epub 2006 Nov 16.

Results Reference

background

PubMed Identifier

16732220

Citation

Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. doi: 10.1038/nrd2060. Epub 2006 May 26.

Results Reference

background

PubMed Identifier

16822958

Citation

Fujii N, Jessen N, Goodyear LJ. AMP-activated protein kinase and the regulation of glucose transport. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E867-77. doi: 10.1152/ajpendo.00207.2006. Epub 2006 Jul 5.

Results Reference

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Effects of Resveratrol in Patients With Type 2 Diabetes

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