Effects of Resveratrol in Patients With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— RED  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01677611
• Other study ID #: NIG 35
• Status: Completed
• Phase: Phase 1
• First received: August 30, 2012
• Last updated: August 31, 2012
• Start date: December 2008
• Est. completion date: March 2012

Study information

• Verified date: August 2012
• Source: Khoo Teck Puat Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences Authority, Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 2012
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 69 Years

Eligibility

Inclusion Criteria:

1. Ability to give informed consent

2. Chinese Male

3. Age 40 to 69 yrs old

4. 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Trans-resveratrol extract from Polygonum Cuspidatum
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.
• Placebo

Locations

Country	Name	City	State
Singapore	Alexandra Health, Khoo Teck Puat Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
Khoo Teck Puat Hospital	National Medical Research Council (NMRC), Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (4)

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. Epub 2006 Nov 1. — View Citation

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

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. Epub 2006 Jul 5. Review. — View 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. Epub 2006 Nov 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skeletal muscle sirtuin 1 (SIRT1) expression		3 months	No
Secondary	Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression		3 months	No
Secondary	Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression		3 months	No
Secondary	Skeletal muscle glucose transporter type 4 (GLUT 4) expression		3 months	No
Secondary	Glycated hemoglobin (HbA1c)		3 months	No
Secondary	Body weight		3 months	No
Secondary	Insulin sensitivity		3 months	No
Secondary	Lipid profile		3 months	No
Secondary	Energy expenditure		3 months	No
Secondary	Physical activity level		3 months	No
Secondary	Abdominal adipose tissue distribution		3 months	No
Secondary	Skeletal muscle fibre type composition		3 months	No
Secondary	Renal function	Serum creatinine	3 months	Yes
Secondary	Liver function	Transaminases	3 months	Yes