DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Valproic Acid and Its Effects on HIV Latent Reservoirs

Information source: McGill University Health Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Valproic Acid (Drug); HAART (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: McGill University Health Center

Official(s) and/or principal investigator(s):
Jean-Pierre Routy, MD, Principal Investigator, Affiliation: Royal-Victoria Hospital/McGill University Health Centre

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.

Clinical Details

Official title: Use of Valproic Acid to Purge HIV From Resting CD4+ Memory Cells/ A Proof-of-Concept Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

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.

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

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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 ┬│ 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.

Locations and Contacts

BC St-Paul's Hospital/Immunodeficiency Clinic, Vancouver, British Columbia V6Z 1Y6, Canada

Ottawa Health Research Institute/Immunodeficiency Clinic, Ottawa, Ontario K1H 8L6, Canada

Actuel Medical Clinic, Montreal, Quebec H2L 4P9, Canada

Montreal Chest Institute/Immunodeficiency Clinic, Montreal, Quebec H2X 2P4, Canada

Quartier Latin Medical Clinic, Montreal, Quebec H2L 5B1, Canada

CHUL Ste-Foy, Ste-Foy, Quebec G1V 4G2, Canada

Additional Information

Canadian HIV Trials Network (CTN)

Starting date: June 2006
Last updated: March 30, 2009

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017