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Study of Valproic Acid to Treat HIV Infected Adults

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ClinicalTrials.gov Identifier: NCT00312546
Recruitment Status : Terminated
First Posted : April 10, 2006
Last Update Posted : May 14, 2012
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
HIV Infections Drug: Enfuvirtide Drug: Valproic acid Phase 1

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Inhibiting Histone Deacetylase: Toward Eradication of HIV
Study Start Date : June 2006
Actual Primary Completion Date : April 2009
Actual Study Completion Date : October 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: 2A
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
Other Name: T-20
Experimental: 2B
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
Experimental: 3A
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
Other Name: T-20
Drug: Valproic acid
500 to 750 mg, taken orally twice daily
Experimental: 3B
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
Other Name: T-20


Outcome Measures
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Primary Outcome Measures :
  1. Frequencies of replication-competent HIV detected in resting CD4 cells [ Time Frame: At pre-entry and Week 0 to Weeks 12 and 16 ]

Secondary Outcome Measures :
  1. Change in integrated proviral genomes [ Time Frame: Throughout study ]
  2. Genital tract proviral DNA and viral load [ Time Frame: Throughout study ]
  3. Detectable viral load during VPA therapy and if it remains undetectable after VPA is discontinued [ Time Frame: Throughout study ]
  4. HIV-specific antibody changes and CTL responses [ Time Frame: From Week 0 to 16 ]
  5. 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 ]
  6. Changes in viral load after intensification of HAART with or without VPA [ Time Frame: Throughout study ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 immunomodulators 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00312546


Locations
United States, North Carolina
University of North Carolina Memorial Hospital
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: David M. Margolis, MD University of North Carolina, Chapel Hill
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00312546     History of Changes
Other Study ID Numbers: U01AI067854-02 ( U.S. NIH Grant/Contract )
CID 0703
7R01AI064074-01A1 ( U.S. NIH Grant/Contract )
7R01AI045297-08 ( U.S. NIH Grant/Contract )
U01A125868
First Posted: April 10, 2006    Key Record Dates
Last Update Posted: May 14, 2012
Last Verified: May 2012

Keywords provided by University of North Carolina, Chapel Hill:
Virus Latency
Valproic Acid
Histone Deacetylase

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Valproic Acid
Enfuvirtide
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents