Free Fatty Acids and Vascular Function in Subjects With Diabetes
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Impact of Free Fatty Acid Reduction on Vascular Function and Skeletal Muscle Glucose Utilization in Type 2 Diabetes Mellitus|
- Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome [ Time Frame: 7 days ] [ Designated as safety issue: No ]Flow mediated dilation is calculated as follows: A resting arterial diameter measurement is obtained using the average of 10 EKG-gated ultrasound images. Next, an occlusive pressure is applied (using a blood pressure cuff inflated to a suprasystolic pressure)for a period of 5 minutes. After 5 minutes, the cuff is rapidly deflated. This produces a reactive hyperemic response which is captured via ultrasound at 1 minute post cuff deflation (also 10 EKG-gated images averaged). The diameter of the artery following reactive hyperemia is calculated and compared to the resting diameter to obtain a percent dilation. This is flow-mediated dilation.
- Difference in Flow-mediated, Endothelium-dependent Brachial Artery Vasodilation Between Test Agent and Placebo [ Time Frame: 7 days ] [ Designated as safety issue: No ]
- Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo [ Time Frame: 7 days ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||March 2013|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
subjects will receive acipimox 250 mg orally every 6 hours (or matching placebo) for 7 days, including a dose at 6am on the morning of the study testing visit
Other Name: Olbetam
Placebo Comparator: 2
During the past two decades, there has been a steady increase in the incidence of diabetes mellitus, such that nearly 17 million people are now afflicted. The vast majority of these have type 2 diabetes. Over the next 40 years, the type 2 diabetic population in the United States is expected to increase to nearly 30 million.
Diabetes substantially increases the risk of atherosclerosis, and thereby, cardiovascular morbidity and mortality. Indeed, cardiovascular disease causes more than 50% of the mortality in patients with diabetes. People with type 2 diabetes manifest two cardinal signs of dysmetabolism: hyperglycemia and insulin resistance. Insulin resistance is a progressive phenomenon that occurs well before the onset of frank diabetes, and results in alterations in insulin signaling. Experimental studies suggest that insulin signaling is required for vascular homeostasis, and its impairment is associated with endothelial dysfunction. In the clinical setting, insulin resistance is associated with atherosclerosis and predicts cardiovascular events independent of hyperglycemia. Therefore, we will study the importance of insulin signaling in endothelial biology in humans and the effects of free fatty acids on endothelial function in people with type 2 diabetes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00153179
|United States, Massachusetts|
|Brigham & Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Mark Creager, M.D.||Brigham and Women's Hospital|