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Free Fatty Acids and Vascular Function in Subjects With Diabetes

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00153179
First Posted: September 12, 2005
Last Update Posted: July 8, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital
  Purpose
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.

Condition Intervention Phase
Type 2 Diabetes Mellitus Drug: acipimox Drug: placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, 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

Further study details as provided by Mark Alan Creager, MD, Brigham and Women's Hospital:

Primary Outcome Measures:
  • Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome [ Time Frame: 7 days ]
    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 ]
  • Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo [ Time Frame: 7 days ]

Enrollment: 110
Study Start Date: September 2005
Study Completion Date: March 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: 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
Other Name: Olbetam
Placebo Comparator: 2
placebo
Drug: placebo
matching placebo

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00153179


Locations
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Mark Creager, M.D. Brigham and Women's Hospital
  More Information

Responsible Party: Mark Alan Creager, MD, Associate Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00153179     History of Changes
Other Study ID Numbers: 2005P-000088
First Submitted: September 8, 2005
First Posted: September 12, 2005
Results First Submitted: March 19, 2013
Results First Posted: July 8, 2013
Last Update Posted: July 8, 2013
Last Verified: May 2013

Keywords provided by Mark Alan Creager, MD, Brigham and Women's Hospital:
insulin resistance
insulin signaling
endothelium-dependent vasodilation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acipimox
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents