- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01676363
Pilot Study of Diflunisal in HIV-infected Adults
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
British Columbia
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Vancouver, British Columbia, Canada
- Immunodeficiency Clinic, St. Paul's Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adult men and women aged 19 years or over
- HIV positive by ELISA and Western blot, at least 3 months prior to screening
- No antiretroviral therapy within 3 months prior to screening
- Plasma HIV RNA (viral load) > 2,500 copies/mL at screening
- Current CD4 cell count >350 cells/mm3 at screening
- Adequate renal function as demonstrated by eGFR >60 mL/min. at screening
Exclusion Criteria:
- Pregnancy or breast-feeding
- Any HIV-associated symptom or condition (e.g. nephropathy) for which standard antiretroviral therapy is indicated immediately
- History of peptic ulcer and/or gastrointestinal bleeding
- Allergy to ASA, other salicylates, or NSAIDs
- Currently receiving treatment with an ACE inhibitor, ASA, anticoagulants, antacids containing aluminum hydroxide, cyclosporine, diuretics, systemic glucocorticoids, lithium, methotrexate, or other NSAIDs
- Significant hepatic impairment or active liver disease - screening AST, ALT, or bilirubin >2.5x upper limit of normal (ULN)
- Hyperkalemia - screening serum potassium >5.5 mmol/L
- Anemia - screening hemoglobin <85 g/L
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Diflunisal
|
Open-label diflunisal 500 mg twice daily for 4 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Plasma HIV RNA changes between baseline and end of 4-week treatment, and between end of treatment and end of 2-week washout
|
between baseline and end of 4-week treatment, and between end of treatment and end of 2-week washout
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical adverse events including serious adverse events
Time Frame: from screening until final study visit on Day 50
|
from screening until final study visit on Day 50
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|
Clinically significant changes in laboratory parameters
Time Frame: between screening and Day 50
|
changes in complete blood count (CBC), platelets; serum creatinine, estimated glomerular filtration rate (GFR); AST, ALT, total bilirubin; serum potassium; CD4 cell count
|
between screening and Day 50
|
Slope of HIV RNA change
Time Frame: during 4-week treatment and 2-week washout phases
|
during 4-week treatment and 2-week washout phases
|
|
Changes in inflammatory biomarkers
Time Frame: during 4-week treatment and 2-week washout phases
|
Changes in C-reactive protein (CRP), d-dimer, possibly other biomarkers
|
during 4-week treatment and 2-week washout phases
|
Changes in T cell subsets
Time Frame: during 4-week treatment and 2-week washout phases
|
Changes in naïve and memory CD4 and CD8 cells
|
during 4-week treatment and 2-week washout phases
|
Changes in protein acetylation (histone or other) in peripheral blood mononuclear cells (PBMCs)
Time Frame: during 4-week treatment and 2-week washout phases
|
during 4-week treatment and 2-week washout phases
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Julio Montaner, MD, Providence Health Care/ University of British Columbia
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Diflunisal
Other Study ID Numbers
- H11-03547 (Other Identifier: UBC/Providence Health Care REB)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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