A Phase 1 interventional study of Enfuvirtide and Valproic acid in HIV Infections, sponsored by University of North Carolina, Chapel Hill. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-05-14.
Sponsored by University of North Carolina, Chapel Hill · Phase 1, Interventional, and Treatment
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.
VPA is a type of medication normally used to treat seizures and other nervous system problems. It has been found that VPA works against HIV by releasing the virus from resting CD4 cells, allowing other anti-HIV medications to attack it. The purpose of this study is to assess the efficacy of VPA when used in HIV infected participants using highly active antiretroviral therapy (HAART). The expected duration of participation for individually enrolled participants will depend on which study group the participant is placed in but may range from approximately 24 to 144 weeks.
An initial screening visit will occur about 30 to 120 days prior to study entry. A physical exam, medical and medication history assessment, and blood and urine collection will occur at screening. Leukapheresis and genital secretion collection will occur once 30 to 120 days prior to study entry, separate from the initial screening.
In Step 1, all participants will receive VPA while continuing their current HAART. Doses of VPA will vary by participant. Study visits will occur on Days 0 and 3 and Weeks 1, 2, 4, 8, 12, 16, and 24. A physical exam and blood and urine collection will occur at most visits. Leukapheresis and genital secretion collection will occur at study entry and Weeks 12 and 16. After 24 weeks, participants will enter Step 2. Those participants not responding to VPA in Step 1 will enroll in Step 2A. Participants responding to VPA in Step 1 will enroll in Step 2B.
In Step 2A, participants will discontinue VPA and will receive intensified therapy (enfuvirtide) administered for 24 weeks twice daily. Study visits will occur at Weeks 25, 28, 32, 36, 40, and 48. A physical exam and blood and urine collection will occur at all visits. Leukapheresis will occur at Weeks 36 and 40. Participants who do not respond to intensified therapy in Step 2A will enroll in Step 3A. Participants who respond to intensified therapy in Step 2A will enroll in Step 3B.
In Step 2B, participants will continue to receive VPA for up to 96 weeks. Study visits will occur every 8 weeks until Week 120. A physical exam and blood and urine collection will occur at each visit. Leukapheresis will occur once between Week 72 and Week 120.
In Step 3A, VPA will be added to enfuvirtide for 16 weeks. The study will be discontinued for participants who do not respond. Study visits will occur at screening, entry, Day 0, and Weeks 1, 2, 4, 8, 12, 16, and 22. A physical exam and blood and urine collection will occur at all visits. Leukapheresis will occur after screening, at entry, Day 0 and Weeks 12 and 16.
In Step 3B, participants may continue receiving enfuvirtide for up to 96 weeks. Study visits will occur every 8 weeks until Week 144. A physical exam and blood and urine collection will occur at each visit. Leukapheresis will occur at Week 96 or 144.
Participants may choose to enter an observational period at any time before they start Step 2 or Step 3. During the observational period, participants continue to take HAART but not VPA or enfuvirtide. Upon entering an observational period, study staff will contact the participant every 8 weeks for a review of their medical records. Each participant will have a study visit within 8 weeks of beginning a new step. These interim study screenings include a physical exam, medical history, and blood and urine collection. Participants may be asked to have additional leukapheresis performed if they have discontinued study medications for 12 weeks or more.
Each leukapheresis procedure will take place at the University of North Carolina Apheresis Clinic in Chapel Hill, North Carolina. This study will not provide participants' current HAART regimen medications.
NOTE: As of 05/20/08, the observational period and Steps 1, 2, 2A, 2B, and 3B were discontinued.
4,257 studies on the registry are indexed under HIV Infections; 240 are open to participants now.
This study's enrollment of 14 is below the median of 83 across 3,250 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.
Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Discontinuation of VPA and enfuvirtide administered for 24 weeks. As of 05/20/08 this step was discontinued.
Drug: Enfuvirtide
Continuation of VPA for up to 96 weeks. As of 05/20/08 this step was discontinued.
Drug: Valproic acid
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 · Drug: Valproic acid
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
Also known as: T-20
500 to 750 mg, taken orally twice daily
Frequencies of replication-competent HIV detected in resting CD4 cells
Time frame: At pre-entry and Week 0 to Weeks 12 and 16
Change in integrated proviral genomes
Time frame: Throughout study
Genital tract proviral DNA and viral load
Time frame: Throughout study
Detectable viral load during VPA therapy and if it remains undetectable after VPA is discontinued
Time frame: Throughout study
HIV-specific antibody changes and CTL responses
Time frame: From Week 0 to 16
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
Changes in viral load after intensification of HAART with or without VPA
Time frame: Throughout study
This study is terminated, as verified in May 2012. You cannot join it, but the record below documents what was studied.
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University of North Carolina, Chapel Hill