HIV InfectionPhase 4NCT01676363
Pilot Study of Diflunisal in HIV-infected Adults
A Phase 4 study testing Diflunisal in people with HIV Infection, run by University of British Columbia at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Diflunisal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2013to 12 Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Immunodeficiency Clinic, St. Paul's Hospital
Vancouver, British Columbia
About this study
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.
Read the 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.
- Conditions
- HIV Infection
- Being tested
- Diflunisal
- Keywords
- diflunisal, anti-inflammatory agents, non-steroidal, antiviral agents
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiflunisalDrug
Open-label diflunisal 500 mg twice daily for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Diflunisal | Experimental | Not described Receives: Drug: Diflunisal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma HIV RNA level
Plasma HIV RNA changes between baseline and end of 4-week treatment, and between end of treatment and end of 2-week washout
Measured: between baseline and end of 4-week treatment, and between end of treatment and end of 2-week washout
Secondary outcomes (6)
Clinical adverse events including serious adverse events
Measured: from screening until final study visit on Day 50
Clinically significant changes in laboratory parameters
changes in complete blood count (CBC), platelets; serum creatinine, estimated glomerular filtration rate (GFR); AST, ALT, total bilirubin; serum potassium; CD4 cell count
Measured: between screening and Day 50
Slope of HIV RNA change
Measured: during 4-week treatment and 2-week washout phases
Changes in inflammatory biomarkers
Changes in C-reactive protein (CRP), d-dimer, possibly other biomarkers
Measured: during 4-week treatment and 2-week washout phases
Changes in T cell subsets
Changes in naïve and memory CD4 and CD8 cells
Measured: during 4-week treatment and 2-week washout phases
Changes in protein acetylation (histone or other) in peripheral blood mononuclear cells (PBMCs)
Measured: during 4-week treatment and 2-week washout phases
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2012 (estimated)
- Study startMar 2013
- Primary completion12 Oct 2016
- Study completion12 Oct 2016
Why it stopped: Insufficient enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Julio Montaner, University of British Columbia
- Investigators
- Julio Montaner, MD, Principal investigator, Providence Health Care/ University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01676363
- Sponsor's protocol ID
- H11-03547
- Other IDs
- H11-03547
- Status last verified
- Oct 2017
- First submitted
- 28 Aug 2012
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Diflunisal in HIV-infected Adults
- ClinicalTrials.gov ID
- NCT01676363
- Acronym / sponsor ID
- H11-03547
- Conditions
- HIV Infection
- Keywords
- diflunisal, anti-inflammatory agents, non-steroidal, antiviral agents
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient enrollment.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- 12 Oct 2016 (actual)
- Study completion
- 12 Oct 2016 (actual)
- First posted
- 30 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Diflunisal | Experimental | Drug: Diflunisal |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiflunisalOpen-label diflunisal 500 mg twice daily for 4 weeks | Drug | Diflunisal |
Primary outcome
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
6 secondary outcomes
Clinical adverse events including serious adverse events
Time frame: from screening until final study visit on Day 50
Clinically significant changes in laboratory parameters
Time frame: between screening and Day 50
Slope of HIV RNA change
Time frame: 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 T cell subsets
Time frame: 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
Results and safety
The study was stopped early (reason given: Insufficient enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julio Montaner, MD principal investigator
Providence Health Care/ University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Diflunisal in people with HIV Infection, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Insufficient enrollment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.