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

HIV Clinical Trial

— Salsalate  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01046682
• Other study ID #: 02-08-02
• Status: Completed
• Phase: Phase 2
• First received: January 11, 2010
• Last updated: December 18, 2014
• Start date: January 2009
• Est. completion date: July 2009

Study information

• Verified date: December 2014
• Source: University Hospital Case Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endothelial Dysfunction
• HIV
• Inflammation
• Insulin Resistance

Intervention

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.

Locations

Country	Name	City	State
United States	University Hospitals Case Medical Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Case Medical Center	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No