Trial record 8 of 32 for:
" February 16, 2011":" March 18, 2011"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]
The Effect of Vorinostat on HIV RNA Expression in the Resting CD4+ T Cells of HIV+ Pts on Stable ART
This study is currently recruiting participants.
Verified September 2013 by University of North Carolina, Chapel Hill
Information provided by (Responsible Party):
David Margolis, MD, University of North Carolina, Chapel Hill
First received: March 17, 2011
Last updated: September 4, 2013
Last verified: September 2013
The purpose of this study is to compare HIV RNA expression and infection within resting cluster of differentiation 4 (CD4)+ cells in HIV-infected patients on stable ART before and after a single exposure to Vorinostat (VOR) and after exposure to short intervals of VOR dosed over several weeks.
- The frequency of detectable HIV RNA expression within resting CD4+ T cells will be increased following single and repeated exposure to VOR, and
- That repeated exposure to VOR will reduce the frequency of HIV infection within resting CD4+ T cells.
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- To compare HIV RNA expression within resting CD4+ cells in HIV-infected patients on stable ART before and after a single exposure to VOR [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
HIV RNA expression per million resting CD4+ T cells at leukapheresis after VOR 400mg vs. leukapheresis on baseline ART.
- To compare the frequency of resting CD4+T cell infection after repeated short interval dosing with VOR. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Step II evaluation leukapheresis on ART and VOR 400mg given 3 times a week for up to 8 weeks vs. pheresis on baseline ART.
Secondary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||March 2015 (Final data collection date for primary outcome measure)
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).
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).
- SAHA, or MK-0683
|Ages Eligible for Study:
||18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- HIV-1 infection
- Men, women age ≥18 years.
- Ability, willingness to give written informed consent.
- Able, willing to provide adequate locator information.
- Karnofsky performance status >70.
- Able, willing to adhere to therapy and adherent to ART.
- Able,willing to comply with time requirements for study visits and evaluations.
- On potent ART, defined as at least 2 nucleoside/nucleotide reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor, integrase inhibitor, or a protease inhibitor, without changes in the 24 weeks immediately prior to entry. Prior changes in or elimination of medications for easier dosing schedule, intolerance, or toxicity are permitted.
- Adequate vascular access for leukapheresis.
- Able to swallow pills without difficulty.
- Plasma HIV-1 RNA never > 50 copies/ml on 2 consecutive occasions for ≥ 6 months while on ART.
- CD4 cell count ≥ 300 cells/µl at screening.
- At least one drug in 3 or more classes to which the virus is sensitive.
- All male study volunteers must agree not to participate in a conception process.
- Must be seronegative for Hep C RNA, Hep B sAg within 90 days of entry
- Must have adequate organ function as indicated by the following lab values:
Hematological: Absolute Neutrophil Count (ANC) ≥ 1,500/mcL Platelets ≥ 125,000/mcL Hgb ≥ 12 g/dL
Coagulation: Prothrombin Time or International Normalized Ratio (INR) ≤ 1.5x upper limit of normal (ULN)
Chemistry: K+ levels Within normal limits Mg++ levels > Lower limits of normal (LLN) but <1.5 x ULN Glucose Screening serum glucose(fasting/non-fasting) below 120 mg/dl.
Renal: Serum creatinine/calculated creatinine clearance* ≤ 1.3 X ULN OR ≥ 60 mL/min for participants with creatinine levels > 1.3 X ULN
Hepatic: Serum total bilirubin Total bilirubin < 1.5 times ULN. If total bilirubin is elevated, direct bilirubin will be measured and the participant will be eligible if the direct bilirubin is < 2 X ULN.
Aspartate amino transferase (AST) (SGOT) and Alanine amino transferase (ALT) (SGPT)≤ 2.0 X ULN Lipase <1.6 X ULN Alkaline Phosphatase ≤ 2.5 X ULN
*Creatinine clearance should be calculated per institutional standard.
- Received blood transfusions or hematopoetic growth factors within 90 days.
- All women unless there is written documentation of menopause (absence of a period for ≥ one year), hysterectomy, oophorectomy, or tubal ligation.
- Use of atazanavir and raltegravir in background antiretroviral regimens.
- Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy; investigational agents; immunomodulators (colony-stimulating factors, growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons); coumadin, warfarin, or other Coumadin derivative anticoagulants.
- Any serious illness requiring systemic treatment or hospitalization, the subject must either complete therapy or be clinically stable on therapy, in the opinion of the site investigator, for at least 90 days prior to entry.
- Compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric illness or a physical illness, e.g., infectious disease. Prisoner recruitment and participation is not permitted.
- Treatment for an active AIDS-defining opportunistic infection within 90 days prior to screening.
- Any history of cardiac rhythm disturbance requiring medical or surgical therapy.
- Any history of acute or chronic pancreatitis.
- Use of the following medications that carry risk of torsades de pointes: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
- Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid within the last 30 days. Potential participants may enroll after a 30-day washout period.
- Known hypersensitivity to the components of VOR or its analogs.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Pregnancy or breast feeding, or expecting to father children within the projected duration of the study.
- Inability to communicate effectively with study personnel. Is the provider or study PI unable, as assessed by the site investigators, to construct a fully active alternative regimen based on previous resistance testing and/or treatment history?
Please refer to this study by its ClinicalTrials.gov identifier: NCT01319383
|The University of North Carolina at Chapel Hill
|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 |
University of North Carolina, Chapel Hill
||David Margolis, MD
||University of North Carolina, Chapel Hill
No publications provided by University of North Carolina, Chapel Hill
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, Coffin JM, Eron JJ, Hazuda DJ, Margolis DM. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482-5. doi: 10.1038/nature11286.
||David Margolis, MD, Principal Investigator, University of North Carolina, Chapel Hill
History of Changes
|Other Study ID Numbers:
||CID 0807, 1U01AI095052-01
|Study First Received:
||March 17, 2011
||September 4, 2013
||United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government
Keywords provided by University of North Carolina, Chapel Hill:
HIV RNA <50 copies/mL
Resting CD4+ T cells
HIV RNA expression
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 04, 2013
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action