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

Study Overview
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Brief Summary
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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.

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

Conditions
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HIV, Endothelial Dysfunction, Inflammation, Insulin Resistance

Intervention / Treatment
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* Drug: Salsalate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older HIV-infected 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 On a stable antiretroviral (ARV) regimen, i.e., on the same ARV for at least 12 weeks prior to study entry No intention to stop or modify ARV regimen during the study period Exclusion Criteria: 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 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 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 Consumption of alcohol on a daily basis Active use of illicit drugs Unable to attend follow-up appointments Allergy to any salicylic acid-containing medication or salsalate AST or ALT > 2 upper limit of normal (ULN) within 6 months prior to study entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Salsalate<br> | Drug: Salsalate<br>* 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.<br>|
| No Intervention: Usual care<br> | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Endothelial dysfunction, Inflammation, Insulin resistance