Valproic Acid and Its Effects on HIV Latent Reservoirs
The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2008 by McGill University Health Center.
Recruitment status was Active, not recruiting
Recruitment status was Active, not recruiting
Sponsor:
McGill University Health Center
Collaborators:
Canadian Foundation for AIDS Research (CANFAR)
CIHR Canadian HIV Trials Network
Information provided by:
McGill University Health Center
ClinicalTrials.gov Identifier:
NCT00289952
First received: February 8, 2006
Last updated: March 30, 2009
Last verified: January 2008
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: Valproic Acid Drug: HAART |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Use of Valproic Acid to Purge HIV From Resting CD4+ Memory Cells/ A Proof-of-Concept Study |
Resource links provided by NLM:
Further study details as provided by McGill University Health Center:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To assess the clinical and biological tolerance of VPA in chronically HIV-infected patients with undetectable viral load. [ Time Frame: 16 or 32 weeks ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- To explore level of T-cell activation after VPA intervention. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 50 |
| Study Start Date: | June 2006 |
| Estimated Study Completion Date: | December 2008 |
| Estimated Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Group 1
HAART + valproic acid for 16 weeks followed by HAART alone for 32 weeks.
|
Drug: Valproic Acid
Oral valproic acid twice daily for 16 or 32 weeks. Dosage varies based on plasma levels.
Drug: HAART
As per standard of care.
|
|
Experimental: Group 2
HAART alone for 16 weeks followed by HAART + valproic acid for 32 weeks.
|
Drug: Valproic Acid
Oral valproic acid twice daily for 16 or 32 weeks. Dosage varies based on plasma levels.
Drug: HAART
As per standard of care.
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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).
- 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.
Exclusion Criteria:
- 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.
- 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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00289952
Locations
| Canada, British Columbia | |
| BC St-Paul's Hospital/Immunodeficiency Clinic | |
| Vancouver, British Columbia, Canada, V6Z 1Y6 | |
| Canada, Ontario | |
| Ottawa Health Research Institute/Immunodeficiency Clinic | |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| Canada, Quebec | |
| Montreal Chest Institute/Immunodeficiency Clinic | |
| Montreal, Quebec, Canada, H2X 2P4 | |
| Actuel Medical Clinic | |
| Montreal, Quebec, Canada, H2L 4P9 | |
| Quartier Latin Medical Clinic | |
| Montreal, Quebec, Canada, H2L 5B1 | |
| CHUL Ste-Foy | |
| Ste-Foy, Quebec, Canada, G1V 4G2 | |
Sponsors and Collaborators
McGill University Health Center
Canadian Foundation for AIDS Research (CANFAR)
CIHR Canadian HIV Trials Network
Investigators
| Principal Investigator: | Jean-Pierre Routy, MD | Royal-Victoria Hospital/McGill University Health Centre |
More Information
Additional Information:
No publications provided by McGill University Health Center
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Jean-Pierre Routy, MD; Principal Investigator, McGill University Health Center |
| ClinicalTrials.gov Identifier: | NCT00289952 History of Changes |
| Other Study ID Numbers: | BMB#05-018 (CTN-205) |
| Study First Received: | February 8, 2006 |
| Last Updated: | March 30, 2009 |
| Health Authority: | Canada: Health Canada |
Keywords provided by McGill University Health Center:
|
HIV infections Histone deacetylase Inhibitor HIV Reservoirs |
Peripheral Blood Mononuclear Cells Valproic Acid Treatment Experienced |
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 Valproic Acid Histone Deacetylase Inhibitors |
Anticonvulsants Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action GABA Agents Neurotransmitter Agents Physiological Effects of Drugs Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs |
ClinicalTrials.gov processed this record on May 22, 2013