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Valproic Acid and Its Effects on HIV Latent Reservoirs

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ClinicalTrials.gov Identifier: NCT00289952
Recruitment Status : Unknown
Verified January 2008 by McGill University Health Centre/Research Institute of the McGill University Health Centre.
Recruitment status was:  Active, not recruiting
First Posted : February 10, 2006
Last Update Posted : April 1, 2009
Sponsor:
Collaborators:
Canadian Foundation for AIDS Research (CANFAR)
CIHR Canadian HIV Trials Network
Information provided by:
McGill University Health Centre/Research Institute of the McGill University Health Centre

Tracking Information
First Submitted Date  ICMJE February 8, 2006
First Posted Date  ICMJE February 10, 2006
Last Update Posted Date April 1, 2009
Study Start Date  ICMJE June 2006
Estimated Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2008)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 9, 2006)
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 patients with undetectable viral load.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2008)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2006)
  • ·To assess the clinical and biological tolerance of VPA in chronically HIV-infected patients with undetectable viral load.
  • ·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.
  • ·To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA.
  • ·To explore level of T-cell activation after VPA intervention.
  • ·To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Valproic Acid and Its Effects on HIV Latent Reservoirs
Official Title  ICMJE Use of Valproic Acid to Purge HIV From Resting CD4+ Memory Cells/ A Proof-of-Concept Study
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: Group 1
    HAART + valproic acid for 16 weeks followed by HAART alone for 32 weeks.
    Interventions:
    • Drug: Valproic Acid
    • Drug: HAART
  • Experimental: Group 2
    HAART alone for 16 weeks followed by HAART + valproic acid for 32 weeks.
    Interventions:
    • Drug: Valproic Acid
    • Drug: HAART
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 9, 2006)
50
Original Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2008
Estimated Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00289952
Other Study ID Numbers  ICMJE BMB#05-018 (CTN-205)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jean-Pierre Routy, MD; Principal Investigator, McGill University Health Center
Study Sponsor  ICMJE McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators  ICMJE
  • Canadian Foundation for AIDS Research (CANFAR)
  • CIHR Canadian HIV Trials Network
Investigators  ICMJE
Principal Investigator: Jean-Pierre Routy, MD Royal-Victoria Hospital/McGill University Health Centre
PRS Account McGill University Health Centre/Research Institute of the McGill University Health Centre
Verification Date January 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP