Free Fatty Acids and Vascular Function in Subjects With Diabetes

NCT ID: NCT00153179

Last Updated: 2018-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2013-03-31

Brief Summary

This study will test the hypothesis that reduction in release of free fatty acids from adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal muscle glucose metabolism in subject with type 2 diabetes.

Detailed Description

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Acipimox treatment for 7 days

Group Type: ACTIVE_COMPARATOR

acipimox

Intervention Type: DRUG

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

2

placebo treatment for 7 days

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

matching placebo

Interventions

acipimox

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

Intervention Type: DRUG

placebo

matching placebo

Intervention Type: DRUG

Other Intervention Names

Olbetam

Eligibility Criteria

Inclusion Criteria

• type 2 diabetes mellitus (as defined by the National Diabetes Data Group)
• normal cardiovascular exam
• non smoker (for 1 year prior to entry)
• Healthy volunteers
• no known medical problems
• normal cardiovascular exam
• fasting glucose < 110 mg/dL
• non-smoker (for 1 year prior to entry)

Exclusion Criteria

Type 2 Diabetics

• untreated hypertension (>140/90 mmHg)
• untreated hypercholesterolemia (LDL > 75th percentile for age)
• cigarette smoking within 1 year
• neuropathy requiring medication
• nephropathy (> 300mg/24 hour urinary albumin, or serum creatinine > 1.4 mg/dL
• abnormal cardiovascular exam
• treatment with thiazolidinedione within 1 year
• post-menopausal women taking hormone replacement therapy

(Note: subjects taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) must stop these medications for 2 weeks prior to taking study drug. If blood pressure rises to >140/90, subjects will be prescribed an alternative medication or be withdrawn from the study.

Healthy Volunteers

• abnormal cardiovascular exam
• use of prescription medications
• fasting glucose > 110mg/dL
• cigarette smoking within 1 year

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mark Alan Creager, MD

Associate Professor of Medicine, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Creager, M.D.

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham & Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2005P-000088

Identifier Type: -

Identifier Source: org_study_id