NCT00289952

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for phase_2 hiv-infections

Timeline
Completed

Started Jun 2006

Longer than P75 for phase_2 hiv-infections

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 8, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 10, 2006

Completed
4 months until next milestone

Study Start

First participant enrolled

June 1, 2006

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

March 15, 2023

Status Verified

March 1, 2023

Enrollment Period

6.5 years

First QC Date

February 8, 2006

Last Update Submit

March 13, 2023

Conditions

HIV Infections

Keywords

HIV infectionsHistone deacetylase InhibitorHIV ReservoirsPeripheral Blood Mononuclear CellsValproic AcidTreatment Experienced

Outcome Measures

Primary Outcomes (1)

  • 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.

    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.

    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.

    48 weeks

  • To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA.

    48 weeks

  • To explore level of T-cell activation after VPA intervention.

    48 weeks

  • To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation.

    48 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

HAART + valproic acid for 16 weeks followed by HAART alone for 32 weeks.

Drug: Valproic AcidDrug: HAART

Group 2

EXPERIMENTAL

HAART alone for 16 weeks followed by HAART + valproic acid for 32 weeks.

Drug: Valproic AcidDrug: HAART

Interventions

Valproic AcidDRUG

Oral valproic acid twice daily for 16 or 32 weeks. Dosage varies based on plasma levels.

Group 1Group 2
HAARTDRUG

As per standard of care.

Group 1Group 2

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

BC St-Paul's Hospital/Immunodeficiency Clinic

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Ottawa Health Research Institute/Immunodeficiency Clinic

Ottawa, Ontario, K1H 8L6, Canada

Location

Actuel Medical Clinic

Montreal, Quebec, H2L 4P9, Canada

Location

Quartier Latin Medical Clinic

Montreal, Quebec, H2L 5B1, Canada

Location

Montreal Chest Institute/Immunodeficiency Clinic

Montreal, Quebec, H2X 2P4, Canada

Location

CHUL Ste-Foy

Ste-Foy, Quebec, G1V 4G2, Canada

Location

Related Publications (2)

  • 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.

    PMID: 23195668DERIVED

  • Routy 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.

    PMID: 22276680DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Valproic AcidAntiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipidsDrug Therapy, CombinationDrug TherapyTherapeutics

Study Officials

  • Jean-Pierre Routy, MD

    Royal-Victoria Hospital/McGill University Health Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Dr Jean-Pierre Routy

Study Record Dates

First Submitted

February 8, 2006

First Posted

February 10, 2006

Study Start

June 1, 2006

Primary Completion

December 1, 2012

Study Completion

December 1, 2012

Last Updated

March 15, 2023

Record last verified: 2023-03

Locations

CA(6)