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

Assessment of the Use of Salsalate to Decrease Endothelial Cell Activation and Inflammation in HIV-infected Adults

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Insulin Resistance; HIV; Endothelial Dysfunction
• Intervention / Treatment: Drug: Salsalate

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Flow Mediated Dilation (FMD) of the Brachial Artery Measured by Ultrasound Over 13 Weeks	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.	Entry and week 13 visits

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: January 11, 2010
• First Submitted That Met QC Criteria: January 11, 2010
• First Posted (Estimate): January 12, 2010

Study Record Updates

• Last Update Posted (Estimate): January 7, 2015
• Last Update Submitted That Met QC Criteria: December 18, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Inflammation; Endothelial dysfunction; Insulin resistance; HIV
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Inflammation; Insulin Resistance; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Salicylsalicylic acid
• Other Study ID Numbers: 02-08-02