Study of Valproic Acid to Treat HIV Infected Adults
This study has been terminated.
Sponsor:
University of North Carolina, Chapel Hill
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00312546
First received: April 6, 2006
Last updated: May 11, 2012
Last verified: May 2012
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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 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Inhibiting Histone Deacetylase: Toward Eradication of HIV |
Resource links provided by NLM:
Further study details as provided by University of North Carolina, Chapel Hill:
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 ]
| Enrollment: | 14 |
| Study Start Date: | June 2006 |
| Study Completion Date: | October 2009 |
| Primary Completion Date: | April 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00312546
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
University of North Carolina, Chapel Hill
Investigators
| Principal Investigator: | David M. Margolis, MD | University of North Carolina, Chapel Hill |
More Information
Publications:
| Responsible Party: | University of North Carolina, Chapel Hill |
| ClinicalTrials.gov Identifier: | NCT00312546 History of Changes |
| Other Study ID Numbers: | U01AI067854-02 CID 0703 7R01AI064074-01A1 7R01AI045297-08 U01A125868 |
| Study First Received: | April 6, 2006 |
| Last Updated: | May 11, 2012 |
| Health Authority: | United States: Federal Government |
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 |
ClinicalTrials.gov processed this record on September 27, 2016