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Sponsored by: |
Brigham and Women's Hospital |
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Information provided by: | Brigham and Women's Hospital |
ClinicalTrials.gov Identifier: | NCT00762827 |
The purpose of the study is to test whether salsalate,an aspirin-like drug, can improve blood vessel function by reducing inflammation caused by insulin resistance, making the development of blockages less common.
We also want to see if salsalate will
Condition | Intervention | Phase |
---|---|---|
Metabolic Syndrome |
Drug: Salsalate Drug: Placebo |
Phase II Phase III |
Study Type: | Interventional |
Study Design: | Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment |
Official Title: | The Impact of Reducing Inflammation on Vascular Function in the Metabolic Syndrome |
Estimated Enrollment: | 150 |
Study Start Date: | November 2005 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
1: Active Comparator
Salsalate
|
Drug: Salsalate
4 grams daily for 28 days
|
2: Placebo Comparator
Placebo
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Drug: Placebo
Matching Placebo
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To test the hypothesis that reductions in intracellular inflammation will restore insulin-mediated and endothelium-dependent vasodilation in subjects with the metabolic syndrome.
Recent demographic trends indicate a dramatic growth in the incidence of obesity and insulin resistance in the United States, highlighting a population at increased risk for the complications of atherosclerosis. The metabolic syndrome, identified as through a collection of risk factors, is associated with increases in adiposity and insulin resistance. Insulin resistance, typically characterized by impaired skeletal muscle glucose uptake, affects tissues other than skeletal muscle, including liver, adipose, and blood vessels. In experimental animal models and humans with insulin resistance, disturbances in insulin signaling consistently lead to decreased bioavailability of endothelium-derived nitric oxide and impaired endothelium-dependent vasodilation. The impact of abnormal insulin signaling on vascular endothelium has not been well characterized in humans in vivo.
Basic studies suggest that insulin receptor medicated activation of the PI 3-kinase pathway is important for normal endothelial nitric oxide synthase function. Abnormalities demonstrated in the metabolic syndrome alter signaling at multiple sites within this pathway, particularly phosphorylation of the serine residue of the insulin receptor substrate. Excess free fatty acid liberation by adipose tissue impairs insulin signaling and activates protein kinase C beta and Inhibitor kappa B kinase beta. Each of these pathobiological disturbances, including excess FFA, heightened PKC-beta activation, and increased inflammatory transcription factor activation serine phosphorylate IRS, cause endothelial dysfunction in humans, and are potential therapeutic targets. Data defining the pathophysiology of endothelial insulin resistance and the importance of these candidate mechanisms in patients is lacking.
The applicants will determine whether inhibition of IKKbeta by salsalate improves endothelium-dependent vasodilation as a consequence of restored endothelial insulin signaling and serine 1177 phosphorylation of eNOS in patients with metabolic syndrome.
Ages Eligible for Study: | 18 Years to 85 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
3 out of 5 of the following:
Exclusion Criteria:
* LDL cholesterol >190 mg/dL
Contact: Robert Copeland-Halperin | 617-732-6320 | rcopeland-halperin@partners.org |
Contact: Todd S Perlstein, MD | 617-525-7168 | tperlstein@partners.org |
United States, Massachusetts | |
Brigham and Women's Hospital | Recruiting |
Boston, Massachusetts, United States, 02115 | |
Contact: Robert Copeland-Halperin 617-732-6320 rcopeland-halperin@partners.org | |
Contact: Todd S Perlstein, MD 617-525-7168 tperlstein@partners.org |
Principal Investigator: | Joshua A Beckman, MD | Brigham and Women's Hospital |
Responsible Party: | Brigham and Women's Hospital ( Joshua A. Beckman, MD ) |
Study ID Numbers: | 2005-P-001875 |
Study First Received: | September 26, 2008 |
Last Updated: | September 26, 2008 |
ClinicalTrials.gov Identifier: | NCT00762827 History of Changes |
Health Authority: | United States: Institutional Review Board |
Excess body weight High blood pressure High levels of cholesterol High blood sugar levels |
Anti-Inflammatory Agents Body Weight Analgesics, Non-Narcotic Salicylsalicylic acid Sodium Salicylate Anti-Inflammatory Agents, Non-Steroidal |
Peripheral Nervous System Agents Analgesics Antirheumatic Agents Inflammation Hypertension |
Anti-Inflammatory Agents Disease Salicylsalicylic acid Physiological Effects of Drugs Pharmacologic Actions Inflammation Pathologic Processes Analgesics, Non-Narcotic |
Sensory System Agents Therapeutic Uses Syndrome Anti-Inflammatory Agents, Non-Steroidal Analgesics Peripheral Nervous System Agents Antirheumatic Agents Central Nervous System Agents |