Safety and Efficacy of Salsalate to Treat Endothelial Dysfunction in HIV-infected Adults (Salsalate)

• ClinicalTrials.gov Identifier: NCT01046682
• Recruitment Status: Completed
• First Posted: January 12, 2010
• Results First Posted: April 9, 2012
• Last Update Posted: January 7, 2015
• Sponsor: University Hospitals Cleveland Medical Center
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Grace McComsey, University Hospitals Cleveland Medical Center

Study Description

Brief Summary:

This is a phase II, open label, randomized-controlled pilot study designed to study both the efficacy and safety of salsalate in decreasing endothelial cell dysfunction, systemic inflammation, and insulin resistance in HIV-infected adults. The investigators hypothesis is that salsalate will reduce inflammation and therefore endothelial cell activation and insulin resistance. The sample size will be 40, with an equal number of people being randomized to one of two groups. The first arm will be randomized to salsalate therapy. The second arm will act as a control group. The study duration will be 13 weeks.

Condition or disease	Intervention/treatment	Phase
HIV; Endothelial Dysfunction; Inflammation; Insulin Resistance	Drug: Salsalate	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Assessment of the Use of Salsalate to Decrease Endothelial Cell Activation and Inflammation in HIV-infected Adults
• Study Start Date: January 2009
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Salsalate	Drug: Salsalate; Salsalate 2 grams orally twice a day for 13 weeks. This is the maximum dosage. During the initial 9 days of the study salsalate dose will be titrated to reach this goal dosage.
No Intervention: Usual care

Outcome Measures

Primary Outcome Measures :

1. Change in Flow Mediated Dilation (FMD) of the Brachial Artery Measured by Ultrasound Over 13 Weeks [ Time Frame: Entry and week 13 visits ]
   Flow mediated dilation (FMD) of the brachial artery was measured by ultrasound. This is a measure of endothelial dependent endothelial cell function. Flow mediated dilation is expressed as a percent change from baseline brachial artery diameter to brachial artery diameter after reactive hyperemia. Reactive hyperemia occurred after occluding the brachial artery with a blood pressure cuff for 5 minutes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 18 years of age or older
2. HIV-infected
3. Evidence of durable virologic suppression, i.e., must have HIV-1 RNA < 400 copies/ml at study entry and for at least 12 weeks prior to entry
4. On a stable antiretroviral (ARV) regimen, i.e., on the same ARV for at least 12 weeks prior to study entry
5. No intention to stop or modify ARV regimen during the study period

Exclusion Criteria:

1. Current pregnancy or breast feeding, or women of child bearing age who refuse or are unable to use appropriate methods for contraception during the study period
2. Any of the following conditions: diabetes (2 fasting glucose levels > 126 mg/dL or confirmed random glucose level > 200), creatinine clearance < 50, aspirin-sensitive asthma, COPD, history of bleeding gastric or duodenal ulcer, hepatic dysfunction, active hepatitis B or C, and any active infectious or inflammatory condition
3. Need for regular use of any of the following medications: salsalate, aspirin, non-steroidal antiinflammatories (NSAIDS), corticosteroids, warfarin or other anticoagulation therapy, phenytoin, valproic acid, carbonic anhydrase inhibitors, lithium, probenecid or sulfinpyrazone
4. Consumption of alcohol on a daily basis
5. Active use of illicit drugs
6. Unable to attend follow-up appointments
7. Allergy to any salicylic acid-containing medication or salsalate
8. AST or ALT > 2 upper limit of normal (ULN) within 6 months prior to study entry

Contacts and Locations

Locations

United States, Ohio

University Hospitals Case Medical Center

Cleveland, Ohio, United States, 44106

Sponsors and Collaborators

University Hospitals Cleveland Medical Center

Bristol-Myers Squibb

Investigators

• Principal Investigator: Grace A Mccomsey, M.D.; University Hospitals Case Medical Center and Case Western Reserve University
• Principal Investigator: Corrilynn O Hileman, MD; Case Western Reserve University

More Information

Publications of Results:

Hileman CO, Carman TL, Gripshover BM, O'Riordan M, Storer NJ, Harrill DE, White CA, McComsey GA. Salsalate is poorly tolerated and fails to improve endothelial function in virologically suppressed HIV-infected adults. AIDS. 2010 Jul 31;24(12):1958-61. doi: 10.1097/QAD.0b013e32833c3251.

• Responsible Party: Grace McComsey, Principal Investigator, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT01046682
• Other Study ID Numbers: 02-08-02
• First Posted: January 12, 2010
• Results First Posted: April 9, 2012
• Last Update Posted: January 7, 2015
• Last Verified: December 2014

Keywords provided by Grace McComsey, University Hospitals Cleveland Medical Center:

HIV; Endothelial dysfunction; Inflammation; Insulin resistance

Additional relevant MeSH terms:

Insulin Resistance; Inflammation; Pathologic Processes; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Salicylsalicylic acid; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents