Pilot Study of Diflunisal in HIV-infected Adults
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of Diflunisal in HIV-infected Adults|
- Change in plasma HIV RNA level [ Time Frame: between baseline and end of 4-week treatment, and between end of treatment and end of 2-week washout ] [ Designated as safety issue: No ]Plasma HIV RNA changes between baseline and end of 4-week treatment, and between end of treatment and end of 2-week washout
- Clinical adverse events including serious adverse events [ Time Frame: from screening until final study visit on Day 50 ] [ Designated as safety issue: Yes ]
- Clinically significant changes in laboratory parameters [ Time Frame: between screening and Day 50 ] [ Designated as safety issue: Yes ]changes in complete blood count (CBC), platelets; serum creatinine, estimated glomerular filtration rate (GFR); AST, ALT, total bilirubin; serum potassium; CD4 cell count
- Slope of HIV RNA change [ Time Frame: during 4-week treatment and 2-week washout phases ] [ Designated as safety issue: No ]
- Changes in inflammatory biomarkers [ Time Frame: during 4-week treatment and 2-week washout phases ] [ Designated as safety issue: No ]Changes in C-reactive protein (CRP), d-dimer, possibly other biomarkers
- Changes in T cell subsets [ Time Frame: during 4-week treatment and 2-week washout phases ] [ Designated as safety issue: No ]Changes in naïve and memory CD4 and CD8 cells
- Changes in protein acetylation (histone or other) in peripheral blood mononuclear cells (PBMCs) [ Time Frame: during 4-week treatment and 2-week washout phases ] [ Designated as safety issue: No ]
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Open-label diflunisal 500 mg twice daily for 4 weeks
Following informed consent, potential subjects will undergo a screening visit to determine study eligibility. Within 2 weeks of screening, they will undergo a Day 1 visit for blood testing. At the Day 8 visit on the following Monday, after study visit procedures have been completed, they will commence taking diflunisal 500 mg twice daily by mouth for 4 weeks (Days 8-36, study treatment period), during which they will be seen once a week for blood tests. Following the last dose of diflunisal which will be taken on the morning of Day 36, they will be seen for blood tests after 1 week off the study drug (Days 43, washout phase), and again for a final visit after 2 weeks off study drug, on Day 50.
Subjects will be instructed to take diflunisal 500 mg by mouth in two doses approximately 12 hours apart (+ or - 1 hour), with or without food. A 2-week supply will be dispensed on Days 8 and 22. Study medication bottles (empty or not) will be returned to the clinic on Days 22 and 36. Pill counts will be performed to assess adherence. Adherence will further be evaluated by measuring diflunisal drug levels in plasma samples collected weekly starting at the baseline visit, and assayed at the end of the study.
After the subject has provided informed consent, a screening visit will be performed including a complete medical history and record of concomitant medications to determine study eligibility. Complete physical exam, CBC, platelet count, serum creatinine and estimated GFR, serum potassium, AST, ALT, total bilirubin, CD4 cell count, and pregnancy test for women of child-bearing potential will be performed at the screening visit and repeated at the final study visit. At each study visit, blood will be drawn for HIV RNA, and a serum sample will be collected and stored for measurement of C-reactive protein (CRP), d-dimer, and possibly other inflammatory biomarkers. Plasma (for diflunisal drug level measurement) and peripheral blood mononuclear cells (PBMC's) will be collected and stored weekly from the baseline visit to Day 50. PBMC's will be frozen and shipped in batches to Eric Verdin, MD at the Gladstone Institute of Virology and Immunology (1650 Owens St San Francisco, CA 94158, USA) for analysis of T cell subsets (naïve, memory CD4 and CD8 T cells) and levels of protein acetylation (histone or other) as a surrogate marker of drug activity. Adverse events and concomitant medications will be recorded at the baseline visit and updated weekly.
After completion of the final study visit, subjects will be compensated for their time in the amount of $500. Subjects who need to discontinue the study early, e.g. due to significant clinical or laboratory adverse events related to the study drug, will receive the full stipend at the end of their participation in the study. Subjects who choose to withdraw from the study early or who are withdrawn for study noncompliance will not be eligible to receive the stipend. Subjects who require ongoing reimbursement for travel expenses to enable them to attend study visits will receive advances on their stipend upon providing receipts for parking, etc.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01676363
|Canada, British Columbia|
|Immunodeficiency Clinic, St. Paul's Hospital|
|Vancouver, British Columbia, Canada|
|Principal Investigator:||Julio Montaner, MD||Providence Health Care/ University of British Columbia|