Effect of Leflunomide on T Cell Proliferation in HIV-Infected Patients
This study will evaluate the effect of leflunomide on the life cycle of a specific immune cell called CD4+ T cell in HIV-infected patients. Leflunomide is approved by the Food and Drug Administration for treating rheumatoid arthritis. It works by blocking cell division in activated T cells. In HIV infection, the HIV virus causes increased activation of T cells. The activated cells become infected and die. Activation may also cause the death of T cells that are not infected with HIV. T cells are necessary for the body to fight infections and cancer. This study will see if leflunomide can block T-cell division and possibly reduce the number of cells that die, reduce the number of cells in which HIV can reproduce, and lead to a lower level of HIV virus in the body.
HIV-infected patients between 18 and 65 years of age who have 1) HIV viral levels of 1,000 copies/mL or more, 2) a CD4+ T-cell count of 350 cells/mm3 or more, and 3) a CD4+ T-cell count that has never been less than 200 cells/mm3 may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, chest x-ray, and electrocardiogram (EKG).
Participants are randomly assigned to take leflunomide or placebo (a substance with no active ingredient) every day for 28 days. They come to the clinic three times during the first 29 days of the study (days 1, 15, and 29) for a physical examination and review of any drug side effects. Patients taking placebo end their participation on day 29. Patients taking leflunomide stop taking the drug on day 29 and begin taking cholestyramine three times a day for 11 days out of the next 14 days to clear the leflunomide from their body. On day 43, they return to the clinic to have their leflunomide level checked to make sure that only very little or none of the drug remains in the body. If the level is low, patients end their participation on or around day 57. If the level remains high, they repeat the cholestyramine treatment.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of Leflunomide on HIV-1 Associated Immune Proliferation In Vivo|
|Study Start Date:||January 2005|
|Study Completion Date:||May 2008|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Increased T cell turnover is one of the main abnormalities observed in HIV infected patients and one of the main mechanisms leading to CD4 lymphopenia. This has led to the hypothesis that medications that act directly to suppress immune activation and normalize T cell turnover, could be used in HIV infection. The purpose of this protocol is to evaluate the effect of the immunomodulatory agent, leflunomide, on CD4+ T cell proliferation in HIV infected adults. HIV infected adults who have stable HIV viral loads and are not taking antiretrovirals will receive leflunomide or placebo for 28 days. CD4+ T cell proliferation will be measured as percent Ki67 expression, and the change in expression from baseline to day 28 will be compared between groups. Various studies measuring immune parameters such as CD4+ and CD8+ T cells counts and level of activation will be collected as well as safety studies and HIV viral loads. The primary study risk is adverse reaction to leflunomide. The study will be double-blinded randomized 2:1 (leflunomide versus placebo) and will be reviewed by a DSMB. Total enrollment for the study will be 18 patients.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|