Clinical trial NCT01677611: Effects of Resveratrol in Patients With Type 2 Diabetes
Official title: Effects of Resveratrol in Patients With Type 2 Diabetes: The RED Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: Resveratrol
SIRT1
AMPK
Lead sponsor: Khoo Teck Puat Hospital
Sponsor class: OTHER
Collaborators: name: National Medical Research Council (NMRC), Singapore
First posted: 2012-09-03
Enrollment: 10
Sex: MALE
Minimum age (years): 40
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Skeletal muscle sirtuin 1 (SIRT1) expression
timeFrame: 3 months
Secondary outcomes:
measure: Skeletal muscle 5'-AMP-activated protein kinase (AMPK) expression
timeFrame: 3 months
measure: Skeletal muscle phosphorylated-AMPK-Thr172 (p-AMPK) expression
timeFrame: 3 months
measure: Skeletal muscle glucose transporter type 4 (GLUT 4) expression
timeFrame: 3 months
measure: Glycated hemoglobin (HbA1c)
timeFrame: 3 months
measure: Body weight
timeFrame: 3 months
measure: Insulin sensitivity
timeFrame: 3 months
measure: Lipid profile
timeFrame: 3 months
measure: Energy expenditure
timeFrame: 3 months
measure: Physical activity level
timeFrame: 3 months
measure: Abdominal adipose tissue distribution
timeFrame: 3 months
measure: Skeletal muscle fibre type composition
timeFrame: 3 months
measure: Renal function
timeFrame: 3 months
measure: Liver function
timeFrame: 3 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Alexandra Health, Khoo Teck Puat Hospital
Study officials:
affiliation: Alexandra Health, Khoo Teck Puat Hospital
name: Kian Peng Goh, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.