Valproic Acid and Its Effects on HIV Latent Reservoirs - Full Text View

Sponsors and Collaborators:	McGill University Health Center Canadian Foundation for AIDS Research (CANFAR) Canadian HIV Trials Network
Information provided by:	McGill University Health Center
ClinicalTrials.gov Identifier:	NCT00289952

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 II

MedlinePlus related topics: AIDS Memory

Drug Information available for: Divalproex sodium Valproic acid Valproate Sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study
Official Title:	Use of Valproic Acid to Purge HIV From Resting CD4+ Memory Cells/ A Proof-of-Concept Study

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
Group 1: Experimental 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.
Group 2: Experimental 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
CHUL Ste-Foy
Ste-Foy, Quebec, Canada, G1V 4G2
Quartier Latin Medical Clinic
Montreal, Quebec, Canada, H2L 5B1
Actuel Medical Clinic
Montreal, Quebec, Canada, H2L 4P9

Sponsors and Collaborators

McGill University Health Center

Canadian Foundation for AIDS Research (CANFAR)

Canadian HIV Trials Network

Investigators

Principal Investigator:

Jean-Pierre Routy, MD

Royal-Victoria Hospital/McGill University Health Centre

More Information

Additional Information:

Canadian HIV Trials Network (CTN) This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	McGill University Health Center ( Jean-Pierre Routy, MD; Principal Investigator )
Study ID Numbers:	BMB#05-018 (CTN-205)
Study First Received:	February 8, 2006
Last Updated:	March 30, 2009
ClinicalTrials.gov Identifier:	NCT00289952 History of Changes
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

Study placed in the following topic categories:

Neurotransmitter Agents
Sexually Transmitted Diseases, Viral
Tranquilizing Agents
Acquired Immunodeficiency Syndrome
Psychotropic Drugs
Central Nervous System Depressants
Antimanic Agents

Valproic Acid
Immunologic Deficiency Syndromes
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Retroviridae Infections
Anticonvulsants

Additional relevant MeSH terms:

Neurotransmitter Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Infection
Valproic Acid
Therapeutic Uses
Retroviridae Infections
RNA Virus Infections
Tranquilizing Agents
Immune System Diseases

Acquired Immunodeficiency Syndrome
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
GABA Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on May 07, 2009