Pilot Study of Diflunisal in HIV-infected Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01676363
Recruitment Status : Terminated (Insufficient enrollment.)
First Posted : August 30, 2012
Last Update Posted : October 27, 2017
Information provided by (Responsible Party):
Julio Montaner, University of British Columbia

Brief Summary:
Diflunisal is an anti-inflammatory drug (like ASA or ibuprofen) that has been used as a painkiller for 20 years. Recent research shows that it may have an anti-HIV effect in the laboratory. Approximately 20 HIV-infected adults who are not receiving antiretroviral therapy will be given diflunisal by mouth twice daily for 4 weeks, at a dose that has been shown to be safe when used to treat pain. Subjects will be monitored closely for safety and will have frequent blood tests during the study to see if the drug has any effect on the level of HIV in their blood.

Condition or disease Intervention/treatment Phase
HIV Infection Drug: Diflunisal Phase 4

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 : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Diflunisal in HIV-infected Adults
Study Start Date : March 2013
Actual Primary Completion Date : October 12, 2016
Actual Study Completion Date : October 12, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Diflunisal

Arm Intervention/treatment
Experimental: Diflunisal Drug: Diflunisal
Open-label diflunisal 500 mg twice daily for 4 weeks

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. Clinical adverse events including serious adverse events [ Time Frame: from screening until final study visit on Day 50 ]
  2. 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

  3. Slope of HIV RNA change [ Time Frame: during 4-week treatment and 2-week washout phases ]
  4. 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

  5. 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

  6. Changes in protein acetylation (histone or other) in peripheral blood mononuclear cells (PBMCs) [ Time Frame: during 4-week treatment and 2-week washout phases ]

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Adult men and women aged 19 years or over
  2. HIV positive by ELISA and Western blot, at least 3 months prior to screening
  3. No antiretroviral therapy within 3 months prior to screening
  4. Plasma HIV RNA (viral load) > 2,500 copies/mL at screening
  5. Current CD4 cell count >350 cells/mm3 at screening
  6. Adequate renal function as demonstrated by eGFR >60 mL/min. at screening

Exclusion Criteria:

  1. Pregnancy or breast-feeding
  2. Any HIV-associated symptom or condition (e.g. nephropathy) for which standard antiretroviral therapy is indicated immediately
  3. History of peptic ulcer and/or gastrointestinal bleeding
  4. Allergy to ASA, other salicylates, or NSAIDs
  5. Currently receiving treatment with an ACE inhibitor, ASA, anticoagulants, antacids containing aluminum hydroxide, cyclosporine, diuretics, systemic glucocorticoids, lithium, methotrexate, or other NSAIDs
  6. Significant hepatic impairment or active liver disease - screening AST, ALT, or bilirubin >2.5x upper limit of normal (ULN)
  7. Hyperkalemia - screening serum potassium >5.5 mmol/L
  8. Anemia - screening hemoglobin <85 g/L

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01676363

Canada, British Columbia
Immunodeficiency Clinic, St. Paul's Hospital
Vancouver, British Columbia, Canada
Sponsors and Collaborators
University of British Columbia
Principal Investigator: Julio Montaner, MD Providence Health Care/ University of British Columbia

Responsible Party: Julio Montaner, Dr. Julio Montaner, University of British Columbia Identifier: NCT01676363     History of Changes
Other Study ID Numbers: H11-03547
H11-03547 ( Other Identifier: UBC/Providence Health Care REB )
First Posted: August 30, 2012    Key Record Dates
Last Update Posted: October 27, 2017
Last Verified: October 2017

Keywords provided by Julio Montaner, University of British Columbia:
anti-inflammatory agents, non-steroidal
antiviral agents

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action