HIV InfectionsPhase 2NCT00289952
Valproic Acid and Its Effects on HIV Latent Reservoirs
A Phase 2 study testing Valproic Acid and HAART in people with HIV Infections, run by Jean-Pierre Routy at 6 sites in Canada.
Trial summary
The purpose of this study is to examine whether the co-administration of valproic acid (Epival®), with highly active antiretroviral therapy (HAART) can reduce the size of HIV latent reservoirs in infected CD4 cells. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Valproic Acid and HAART
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 6 sitesCanada
- Study dates
- Jun 2006to Dec 2012
- Phase
- Phase 2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV seropositive infection by Western Blot, EIA assays or viral load.
- Aged 18 years old or older.
- Viral load <50 copies/ml for at least the previous 12 months.
- Circulating CD4+ cell count ³ 200 cells/ml.
- Taking HAART.
- Vital signs, physical examination and laboratory results do not exhibit evidence of diseases such as advanced cirrhosis and advanced liver disease (ALT or AST > 5 x upper limit of normal value).
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- Karnofsky performance status 80%.
- Subject does not require and agrees not to take, for the duration of the study, any medication that is contraindicated with VPA.
- Willing and able to give informed consent.
- All participants will agree to abstinence or to used effective methods of contraception while on the study.
Who cannot join
- Pregnant or breast-feeding women.
- Psychiatric or cognitive disturbance or illness that could preclude compliance with the study.
- Current use or use within four weeks prior to the baseline visit, of cytotoxic agents, systemic corticosteroids or any immunomodulatory agents such as intravenous immunoglobulin, or hydroxyurea.
- HIV vaccine within six months of screening visit
- Allergic reaction to VPA.
- Active intravenous drug users.
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- History of bleeding disorders.
- Unstable or treated hypertension.
- Past-history of pancreatitis or chronic liver disease (ALT or AST > 5 x upper limit of normal value). However subject co-infected with hepatitis B or C can participate if ALT or AST is < 5 x upper limit of normal value.
- Renal failure (creatinine > 2 x upper limit of normal value).
- Ammonemia (> 2x upper limit of normal value).
- Taking Zidovudine (AZT), or combination of drugs containing AZT like Combivir or Trizivir. However this subject will be asked to switch to another NRTI,at least two weeks prior to Valproic Acid initiation, to become eligible.
- Taking on daily basis: phenytoin, carbamazepine, phenobarbital, warfarin or aspirin.
- Subject has any of the following abnormal laboratory results Hemoglobin < 100 g/L. Absolute neutrophil count < 0.75 x 10 9 cells/L. Platelet count < 50 x 10 9 cells/L.
- Subject suffering from urea cycle disorders.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Canada6 sites
Actuel Medical Clinic
Montreal, Quebec, H2L 4P9
Quartier Latin Medical Clinic
Montreal, Quebec, H2L 5B1
Montreal Chest Institute/Immunodeficiency Clinic
Montreal, Quebec, H2X 2P4
Ottawa Health Research Institute/Immunodeficiency Clinic
Ottawa, Ontario, K1H 8L6
CHUL Ste-Foy
Ste-Foy, Quebec, G1V 4G2
BC St-Paul's Hospital/Immunodeficiency Clinic
Vancouver, British Columbia, V6Z 1Y6
About this study
Official title: Use of Valproic Acid to Purge HIV From Resting CD4+ Memory Cells/ A Proof-of-concept Study
The purpose of this study is to examine whether the co-administration of valproic acid (Epival®), with highly active antiretroviral therapy (HAART) can reduce the size of HIV latent reservoirs in infected CD4 cells.
Read the detailed description
Participants must be on HAART with a suppressed viral load (< 50 copies/ml) for at least the previous 12 months. They will be randomly assigned to one of two groups, one group will start the valproic acid right away at week 1 for 16 weeks, and the other group will wait until week 17 to add valproic acid to their treatment for 32 weeks. Subjects will be followed every four weeks for one year and evaluated by a variety of assays, all carried out using well-established methods, to assess the main outcome defined by changes in HIV reservoir size measured by the mean frequency of resting CD4 memory cells carrying HIV proviral DNA.
- Conditions
- HIV Infections
- Being tested
- Valproic Acid, HAART
- Keywords
- HIV infections, Histone deacetylase Inhibitor, HIV Reservoirs, Peripheral Blood Mononuclear Cells, Valproic Acid, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
Oral valproic acid twice daily for 16 or 32 weeks. Dosage varies based on plasma levels.
HAARTDrug
As per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | HAART + valproic acid for 16 weeks followed by HAART alone for 32 weeks. Receives: Drug: Valproic Acid; Drug: HAART |
| Group 2 | Experimental | HAART alone for 16 weeks followed by HAART + valproic acid for 32 weeks. Receives: Drug: Valproic Acid; Drug: HAART |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the effect of VPA on HIV reservoirs measured by the frequency of resting CD4+ memory cells carrying HIV proviral DNA in peripheral blood of chronically HIV-infected subjects.
Measured: 16 or 32 weeks
Secondary outcomes (5)
To assess the clinical and biological tolerance of VPA in chronically HIV-infected patients with undetectable viral load.
Measured: 16 or 32 weeks
To explore the changes in CD4/CD8 ratio, as the size of reservoir is thought to be inversely correlated with the frequency of resting CD4+ memory cells carrying HIV proviral DNA.
Measured: 48 weeks
To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA.
Measured: 48 weeks
To explore level of T-cell activation after VPA intervention.
Measured: 48 weeks
To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2006 (estimated)
- Study startJun 2006
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jean-Pierre Routy
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Foundation for AIDS Research (CANFAR), CIHR Canadian HIV Trials Network
- Responsible party
- Sponsor-investigator, Jean-Pierre Routy, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Jean-Pierre Routy, MD, Principal investigator, Royal-Victoria Hospital/McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00289952
- Sponsor's protocol ID
- BMB#05-018 (CTN-205)
- Status last verified
- Mar 2023
- First submitted
- 8 Feb 2006
- Last updated
- 15 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Routy JP, Angel JB, Spaans JN, Trottier B, Rouleau D, Baril JG, Harris M, Trottier S, Singer J, Chomont N, Sekaly RP, Tremblay CL. Design and implementation of a randomized crossover study of valproic acid and antiretroviral therapy to reduce the HIV reservoir. HIV Clin Trials. 2012 Nov-Dec;13(6):301-7. doi: 10.1310/hct1306-301.
PubMed 23195668Routy JP, Tremblay CL, Angel JB, Trottier B, Rouleau D, Baril JG, Harris M, Trottier S, Singer J, Chomont N, Sekaly RP, Boulassel MR. Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 2012 May;13(5):291-6. doi: 10.1111/j.1468-1293.2011.00975.x. Epub 2012 Jan 26.
PubMed 22276680
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Valproic Acid to Purge HIV From Resting CD4+ Memory Cells/ A Proof-of-concept Study
- ClinicalTrials.gov ID
- NCT00289952
- Acronym / sponsor ID
- BMB#05-018 (CTN-205)
- Conditions
- HIV Infections
- Keywords
- HIV infections, Histone deacetylase Inhibitor, HIV Reservoirs, Peripheral Blood Mononuclear Cells, Valproic Acid, Treatment Experienced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Jean-Pierre RoutyUniversity, hospital or other
- Collaborators
- Canadian Foundation for AIDS Research (CANFAR), CIHR Canadian HIV Trials Network
- Study start
- Jun 2006
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 10 Feb 2006 (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.
The purpose of this study is to examine whether the co-administration of valproic acid (Epival®), with highly active antiretroviral therapy (HAART) can reduce the size of HIV latent reservoirs in infected CD4 cells.
Detailed description
Participants must be on HAART with a suppressed viral load (< 50 copies/ml) for at least the previous 12 months. They will be randomly assigned to one of two groups, one group will start the valproic acid right away at week 1 for 16 weeks, and the other group will wait until week 17 to add valproic acid to their treatment for 32 weeks. Subjects will be followed every four weeks for one year and evaluated by a variety of assays, all carried out using well-established methods, to assess the main outcome defined by changes in HIV reservoir size measured by the mean frequency of resting CD4 memory cells carrying HIV proviral DNA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Valproic Acid, Drug: HAARTHAART + valproic acid for 16 weeks followed by HAART alone for 32 weeks. |
| Group 2 | Experimental | Drug: Valproic Acid, Drug: HAARTHAART alone for 16 weeks followed by HAART + valproic acid for 32 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Documented HIV seropositive infection by Western Blot, EIA assays or viral load.
- Aged 18 years old or older.
- Viral load <50 copies/ml for at least the previous 12 months.
- Circulating CD4+ cell count ³ 200 cells/ml.
- Taking HAART.
Key exclusion criteria (15 listed)
- Pregnant or breast-feeding women.
- Psychiatric or cognitive disturbance or illness that could preclude compliance with the study.
- Current use or use within four weeks prior to the baseline visit, of cytotoxic agents, systemic corticosteroids or any immunomodulatory agents such as intravenous immunoglobulin, or hydroxyurea.
- HIV vaccine within six months of screening visit
- Allergic reaction to VPA.
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 |
|---|---|---|
| Valproic AcidOral valproic acid twice daily for 16 or 32 weeks. Dosage varies based on plasma levels. | Drug | Group 1, Group 2 |
| HAARTAs per standard of care. | Drug | Group 1, Group 2 |
Primary outcome
To assess the effect of VPA on HIV reservoirs measured by the frequency of resting CD4+ memory cells carrying HIV proviral DNA in peripheral blood of chronically HIV-infected subjects.
Time frame: 16 or 32 weeks
5 secondary outcomes
To assess the clinical and biological tolerance of VPA in chronically HIV-infected patients with undetectable viral load.
Time frame: 16 or 32 weeks
To explore the changes in CD4/CD8 ratio, as the size of reservoir is thought to be inversely correlated with the frequency of resting CD4+ memory cells carrying HIV proviral DNA.
Time frame: 48 weeks
To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA.
Time frame: 48 weeks
To explore level of T-cell activation after VPA intervention.
Time frame: 48 weeks
To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation.
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
- Derived from this study: PubMed 23195668Routy JP, Angel JB, Spaans JN, Trottier B, Rouleau D, Baril JG, Harris M, Trottier S, Singer J, Chomont N, Sekaly RP, Tremblay CL. Design and implementation of a randomized crossover study of valproic acid and antiretroviral therapy to reduce the HIV reservoir. HIV Clin Trials. 2012 Nov-Dec;13(6):301-7. doi: 10.1310/hct1306-301.
- Derived from this study: PubMed 22276680Routy JP, Tremblay CL, Angel JB, Trottier B, Rouleau D, Baril JG, Harris M, Trottier S, Singer J, Chomont N, Sekaly RP, Boulassel MR. Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 2012 May;13(5):291-6. doi: 10.1111/j.1468-1293.2011.00975.x. Epub 2012 Jan 26.
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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.
Jean-Pierre Routy, MD principal investigator
Royal-Victoria Hospital/McGill University Health Centre
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Valproic Acid and HAART in people with HIV Infections, run by Jean-Pierre Routy at 6 sites 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 10 inclusion and 15 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: finished, as of the sponsor's last update on 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the effect of VPA on HIV reservoirs measured by the frequency of resting CD4+ memory cells carrying HIV proviral DNA in peripheral blood of chronically HIV-infected subjects. (time frame: 16 or 32 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00289952, which also lists 2 linked publications.
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 15 Mar 2023.