Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk
The hypothesis is that salsalate therapy may be an effective and safe method to modulate inflammation in metabolically-critical tissues and thus reduce insulin resistance and its related complications.
The objectives of the study are to (1) determine whether salsalate therapy improves insulin resistance in subjects with IGT and changes in glucose area under the curve following a standard oral glucose tolerance test (OGTT); (2) determine whether salsalate therapy reduces a) plasma levels of a variety of well established inflammatory proteins and b) mononuclear cell inflammatory activity to provide evidence of reduced systemic and tissue inflammation, respectively; and (3)also determine whether salsalate therapy improves parameters of cardiovascular disease risk, including features of metabolic syndrome (fasting glucose, triglycerides, HDL, and blood pressure) as well as endothelial dysfunction.
|Atherosclerosis Cardiovascular Disease Inflammation Insulin Resistance Noninsulin-dependent Diabetes Mellitus||Drug: Salsalate Drug: Placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk|
- Change in Systemic Glucose Disposal- Glucose Infusion Rates [ Time Frame: 3 months ]Participants were admitted to the Clinical Research Units at 06:00-08:00 hours after an overnight fast. Euglycaemic-hyperinsulinaemic clamps were conducted at baseline and at the end of the study. Because salsalate therapy appears to decrease insulin clearance leading to higher circulating insulin levels during the clamp, we reduced the infusion rate of insulin in the active treatment arm by 20% (from 100 to 80 mUm−2 min−1) at the study end. Insulin solutions were prepared by the site pharmacist so that study staff remained blinded to drug assignment. Whole-body insulin sensitivity was estimated from glucose infusion rate (GIR) during last 30 min of insulin infusions.
- Glucose Area Under the Curve in These Subjects [ Time Frame: 3 months ]
- Plasma Levels of a Variety of Inflammatory Proteins [ Time Frame: 8 and 12 weeks ]
- Parameters of Cardiovascular Disease Risk, Including Glucose, Triglycerides, HDL and Blood Pressure [ Time Frame: 8 and 12 weeks ]
- Endothelial Dysfunction [ Time Frame: 8 and 12 weeks ]
|Study Start Date:||January 2007|
|Study Completion Date:||September 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Placebo Comparator: Arm 1
Active Comparator: Arm 2
Please refer to this study by its ClinicalTrials.gov identifier: NCT00330733
|United States, Arizona|
|Carl T. Hayden VA Medical Center|
|Phoenix, Arizona, United States, 85012|
|Principal Investigator:||Peter Reaven, MD||Carl T. Hayden VA Medical Center|