Study of Valproic Acid to Treat HIV Infected Adults - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) The University of North Carolina, Chapel Hill
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00312546

Purpose

A histone deacetylase (HDAC) inhibitor is a class of drug that interferes with the function of HDAC, an enzyme that hides HIV within inactive CD4 cells. These drugs are normally used to treat seizures and other nervous system problems but have been found to work against HIV. The purpose of this study is to investigate the efficacy of valproic acid (VPA), an HDAC inhibitor, in treating HIV infected adults using anti-HIV drugs.

Condition	Intervention	Phase
HIV Infections	Drug: Enfuvirtide Drug: Valproic acid	Phase II

MedlinePlus related topics: AIDS

Drug Information available for: Divalproex sodium Valproate Sodium Valproic acid Enfuvirtide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study
Official Title:	Inhibiting Histone Deacetylase: Toward Eradication of HIV

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Frequencies of replication-competent HIV detected in resting CD4 cells [ Time Frame: At pre-entry and Week 0 to Weeks 12 and 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in integrated proviral genomes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Genital tract proviral DNA and viral load [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Detectable viral load during VPA therapy and if it remains undetectable after VPA is discontinued [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
HIV-specific antibody changes and CTL responses [ Time Frame: From Week 0 to 16 ] [ Designated as safety issue: No ]
Change in replication-competent HIV detected in resting CD4 cells in study participants after intensified HAART, and after extended VPA therapy with or without intensified HAART [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Changes in viral load after intensification of HAART with or without VPA [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	4
Study Start Date:	June 2006
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2A: Experimental Discontinuation of VPA and enfuvirtide administered for 24 weeks. As of 05/20/08 this step was discontinued.	Drug: Enfuvirtide 90 mg subcutaneously twice daily
2B: Experimental Continuation of VPA for up to 96 weeks. As of 05/20/08 this step was discontinued.	Drug: Valproic acid 500 to 750 mg, taken orally twice daily
3A: Experimental VPA may be added to enfuvirtide for 16 weeks. VPA and enfuvirtide will be continued for up to 96 weeks in responders, and the study will be discontinued in nonresponders.	Drug: Enfuvirtide 90 mg subcutaneously twice daily Drug: Valproic acid 500 to 750 mg, taken orally twice daily
3B: Experimental Enfuvirtide may be continued for up to 96 weeks. As of 05/20/08 this step was discontinued.	Drug: Enfuvirtide 90 mg subcutaneously twice daily

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Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infected
Adherent to current HAART regimen
Adequate vascular access for leukapheresis
Receiving HAART, defined as at least two nucleoside reverse transcriptase inhibitors plus at least one protease inhibitor or non-nucleoside reverse transcriptase inhibitor, without changes to the regimen within 24 weeks of study entry
Viral load more than 50 copies/ml on two consecutive occasions for more than 6 months, and less than 200 copies/ml on occasion for more than 6 months prior to study entry
CD4 count more than 300 cells/mm3
Willing and able to comply with all study requirements
Willing to use acceptable forms of contraception

Exclusion Criteria:

Currently receiving zidovudine or enfuvirtide
Require certain medications known to interact with valproate (e.g., lamotrigine; barbiturates; carbamazepine; prescription dosages of salicylates, hydantoins, felbamate, and clonazepam)
Any medical, psychiatric, or job-related responsibility that would interfere with the study. More information about this criterion can be found in the protocol.
Contraindications to taking VPA (e.g., pregnancy, bleeding disorders, history of pancreatitis, history of hepatitis)
Receiving interferon, other immunomodulators, or other experimental medications
Abnormal liver enzyme tests
Hepatitis B virus infected
Symptoms of hepatic decompensation
Blood transfusions or hematopoietic growth factors within 90 days prior to study entry
Systemic cytotoxic chemotherapy, investigational agents, or immunodulators within 90 days prior to study entry
Current drug or alcohol abuse that, in the opinion of the site investigator, would interfere with the study
Serious illness requiring systemic treatment or hospitalization within 90 days prior to study entry
Treatment for a current AIDS-defining opportunistic infection within 90 days prior to screening
Anemic
Involuntarily incarcerated for treatment of either a psychiatric illness or physical illness (e.g., infectious disease)
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312546

Locations

United States, North Carolina
University of North Carolina Memorial Hospital
Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

The University of North Carolina, Chapel Hill

Investigators

Principal Investigator:

David M. Margolis, MD

The University of North Carolina, Chapel Hill

More Information

Click here for more information on valproic acid This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Jiang G, Espeseth A, Hazuda DJ, Margolis DM. c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J Virol. 2007 Oct;81(20):10914-23. Epub 2007 Aug 1.

Siliciano JD, Lai J, Callender M, Pitt E, Zhang H, Margolick JB, Gallant JE, Cofrancesco J Jr, Moore RD, Gange SJ, Siliciano RF. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J Infect Dis. 2007 Mar 15;195(6):833-6. Epub 2007 Jan 30.

Smith SM. Valproic acid and HIV-1 latency: beyond the sound bite. Retrovirology. 2005 Sep 19;2:56.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	U01AI067854-02, CID 0703, 7R01AI64074-01A1, 7R01AI45297-08, U01A125868
Study First Received:	April 6, 2006
Last Updated:	December 30, 2008
ClinicalTrials.gov Identifier:	NCT00312546
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Virus Latency
Valproic Acid
Histone Deacetylase

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome

Valproic Acid
Retroviridae Infections
Enfuvirtide
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
Neurotransmitter Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors

Infection
Antimanic Agents
Antiviral Agents
Pharmacologic Actions
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
GABA Agents
Central Nervous System Agents
Anticonvulsants
HIV Fusion Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009