Clinical trial NCT01046682: Safety and Efficacy of Salsalate to Treat Endothelial Dysfunction in HIV-infected Adults
Official title: Assessment of the Use of Salsalate to Decrease Endothelial Cell Activation and Inflammation in HIV-infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Endothelial Dysfunction
Inflammation
Insulin Resistance
Keywords: HIV
Endothelial dysfunction
Inflammation
Insulin resistance
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2010-01-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change in Flow Mediated Dilation (FMD) of the Brachial Artery Measured by Ultrasound Over 13 Weeks
timeFrame: Entry and week 13 visits
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Case Medical Center and Case Western Reserve University
name: Grace A Mccomsey, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Corrilynn O Hileman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.