The Effect of Vorinostat on HIV RNA Expression in the Resting CD4+ T Cells of HIV+ Pts on Stable ART
The purpose of this study is to compare HIV RNA expression and infection within resting (CD4)+ cells in HIV-infected patients on stable ART before and after a single exposure to Vorinostat (VOR), after exposure to short intervals of VOR, and after repeated short interval exposure to VOR dosed over several weeks.
- The frequency of resting CD4+ T cell- associated HIV RNA (RCVL) will be increased following single and repeated exposure to VOR when given at appropriate intervals, and
- That repeated exposure to VOR will reduce the frequency of HIV infection within resting CD4+ T cells (RCI)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Investigation of the Effect of Vorinostat (VOR) on HIV RNA Expression in the Resting CD4+ T Cells of HIV-Infected Patients Receiving Stable Antiretroviral Therapy|
- To compare RCVL in HIV-infected patients on stable ART, before and after a single exposure to VOR, after a pair of exposures to VOR, and after multiple exposures to VOR. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]HIV RNA expression per 1 million resting CD4+ cells (RCVL) after the second of a pair of VOR doses, in participants who exhibited an increase in HIV RNA expression per 1 million resting CD4+ cells after a single 400 mg dose of VOR (HIV RNA per million resting CD4+ T cells). We will compare the HIV RNA expression per 1 million resting CD4+ cells obtained at the leukapheresis after paired VOR doses to the level obtained at baseline leukapheresis on stable ART.
- To compare the change in HIV RNA expression per million resting CD4 + cells after multiple (10) VOR doses. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]HIV RNA per million resting CD4+ T cells at leukapheresis after ten 400 mg VOR doses vs. level at baseline leukapheresis on stable ART.
- Changes on plasma HIV-1 RNA [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]By standard assay and single copy assay.
- To assess safety, tolerability, and PK profile of VOR [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- To assess the alterations in global histone acetylation within resting lymphocytes [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To compare the frequency of resting CD4+ T cell infection (RCI) after multiple (10) repeated short interval dosing with VOR [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]Leukapheresis on ART and VOR vs. leukapheresis on baseline ART
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Step 1 - Screening (Visit 1), Enrollment (Visit 2) and Single Dose Vorinostat 400 mg (Visits 3 & 4)
Step 2 - Visits 5 and 6 - Paired Doses of Vorinostat 400 mg and Leukapheresis.
Step 3: Visits 8 - 13 Multiple Doses of Vorinostat 400 mg and Leukapheresis
Drug administration - Step 1 - 400mg Vorinostat will be given as single doses by mouth at visits 2 and 5.
Step II - 400 mg VOR for 3 consecutive days a week (for a maximum of 8 weeks).
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|Contact: JoAnn Kuruc, MSN, RNfirstname.lastname@example.org|
|United States, North Carolina|
|The University of North Carolina at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27514|
|Contact: JoAnn Kuruc, MSN, RN 919-966-8533 email@example.com|
|Principal Investigator: David Margolis, MD|
|Sub-Investigator: Joseph Eron, MD|
|Sub-Investigator: Christopher Hurt, MD|
|Principal Investigator:||David Margolis, MD||University of North Carolina, Chapel Hill|