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

NCT01046682 | Completed Phase 2 Results

• 1 other identifier: 02-08-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV; Endothelial Dysfunction; Inflammation; Insulin Resistance

Keywords

HIV; Endothelial dysfunction; Inflammation; Insulin resistance

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Salsalate

ACTIVE COMPARATOR

Drug: Salsalate

Usual care

NO INTERVENTION

Interventions

Salsalate DRUG

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.

Salsalate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Related 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: 10.1097/QAD.0b013e32833c3251.

  PMID: 20613460 RESULT

MeSH Terms

Conditions

Inflammation; Insulin Resistance

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Lack of placebo in the control group precluded blinding of the study investigators. Adherence was measured utilizing pill counts which assumes that pills not returned were taken by the participant. Sample size too small to detect a small effect.

Results Point of Contact

• Title: Grace McComsey, MC
• Organization: UHospitalsCleveland

mccomsey.grace@clevelandactu.org

216-844-3607

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 12, 2010
• Study Start: January 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: January 7, 2015
• Results First Posted: April 9, 2012

Record last verified: 2014-12

Locations

US (1)