Valproic Acid and Its Effects on HIV Latent Reservoirs

March 13, 2023 updated by: Jean-Pierre Routy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • BC St-Paul's Hospital/Immunodeficiency Clinic
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Health Research Institute/Immunodeficiency Clinic
    • Quebec
      • Montreal, Quebec, Canada, H2L 4P9
        • Actuel Medical Clinic
      • Montreal, Quebec, Canada, H2L 5B1
        • Quartier Latin Medical Clinic
      • Montreal, Quebec, Canada, H2X 2P4
        • Montreal Chest Institute/Immunodeficiency Clinic
      • Ste-Foy, Quebec, Canada, G1V 4G2
        • CHUL Ste-Foy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
16 or 32 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the clinical and biological tolerance of VPA in chronically HIV-infected patients with undetectable viral load.
Time Frame: 16 or 32 weeks
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
48 weeks
To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA.
Time Frame: 48 weeks
48 weeks
To explore level of T-cell activation after VPA intervention.
Time Frame: 48 weeks
48 weeks
To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation.
Time Frame: 48 weeks
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jean-Pierre Routy

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

February 8, 2006

First Submitted That Met QC Criteria

February 9, 2006

First Posted (Estimate)

February 10, 2006

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BMB#05-018 (CTN-205)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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