Trial record 14 of 30 for:    " August 01, 2012":" August 31, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Pilot Study of Diflunisal in HIV-infected Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of British Columbia
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01676363
First received: August 28, 2012
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
HIV Infection
Drug: Diflunisal
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diflunisal Drug: Diflunisal
Open-label diflunisal 500 mg twice daily for 4 weeks

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01676363

Contacts
Contact: Marianne Harris, MD 604-806-8771 mharris@cfenet.ubc.ca

Locations
Canada, British Columbia
Immunodeficiency Clinic, St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada
Contact: Marianne Harris, MD    604-806-8771    mharris@cfenet.ubc.ca   
Principal Investigator: Julio Montaner, MD         
Sub-Investigator: Marianne Harris, MD         
Sub-Investigator: Silvia Guillemi, MD         
Sub-Investigator: Mark Hull, MD         
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Julio Montaner, MD Providence Health Care/ University of British Columbia
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01676363     History of Changes
Other Study ID Numbers: H11-03547, H11-03547
Study First Received: August 28, 2012
Last Updated: July 2, 2014
Health Authority: Canada: Health Canada

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

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

ClinicalTrials.gov processed this record on October 19, 2014