Effect of Leflunomide on T Cell Proliferation in HIV-Infected Patients

Completed · Phase 1

Conditions studied: HIV Infections

In brief

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.

Key facts

Study ID

NCT00101374

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

41

Starts

2005-01-05

Expected to finish

2008-05-21

Last updated by the study team

2017-07-02

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Current treatment with antiretrovirals or use of antiretrovirals within 12 weeks of screening.
• Intention of start antiretroviral regimen within 64 day study period.
• Previous treatment with leflunomide.
• Previous treatment with IL-2.
• Treatment with immunomodulatory agents (including hydroxyurea, mycophenolate, cyclosporine, rapamycin, anti-HIV vaccines, interleukins other than IL-2, interferons) within 60 days of study.
• Treatment with systemic corticosteroids within 30 days of study.
• Inability or unwillingness to discontinue drugs (except NSAIDS) that are metabolized by P450 2C9 isoenzyme (see Appendix A- Medications Metabolized by CYP 2C9 and Contraindicated During Treatment Period).
• Inability or unwillingness to discontinue hepatotoxic drugs (eg. isoniazid, rifampin, HMG CoA reductase inhibitors).
• Inability or unwillingness to discontinue drug that interact with cholestyramine (eg. have diminished absorption with cholestyramine) (see Appendix B- Medications that have Interactions with Cholestyramine).
• Current use of or known intolerance of cholestyramine or bile acid sequestering resins.
• History of familial hyperlipoproteinemia type III, IV or V.
• Active bacterial infection within 4 weeks of screening.
• History of AIDS-defining illness (category C) (see Appendix C - CDC AIDS Classification Criteria).
• Hepatitis B or C infection.
• Acute or chronic liver disease from any cause (eg. alcoholic hepatitis or alcohol induced cirrhosis, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, Wilson's disease, hemochromatosis) which the investigator feels would compromise the subject's safety.
• History of biliary obstruction.
• Current alcohol abuse or unwillingness to abstain from alcohol use for study period.
• History of hypertension that is not controlled (less than 140/80 mm/Hg) on a single antihypertensive agent.
• Abnormal laboratory findings: hemoglobin less than 10 g/dL; ANC less than 1000/mm(3); platelets less than 100,000/mm(3); creatine above the upper limit of normal; ALT or alkaline phosphatase greater than 1.25 times the upper limit of normal; AST greater than 1.25 times the upper limit of normal (subjects with isolated AST elevation, higher than normal CPK values in the absence of liver disease and compatible history such as intense exercise will be allowed to re-screen if the study investigators suspect that the elevated AST is of muscular origin) direct bilirubin greater than 1.5 times the upper limit of normal; total bilirubin greater than 2 times the upper limit of normal lipase greater than 1.5 times the upper limit of normal; PT greater than 1.1 times the upper limit of normal; PTT greater than 1.5 times the upper limit of normal.
• History of malignant neoplasm except in situ anogenital carcinoma, adequately treated basal or squamous cell carcinoma of the skin or solid tumors treated with curative therapy and disease free for at least five years.
• Significant medical or psychiatric disorder which the investigator feels would interfere with the subject's ability to participate or would compromise safety.
• Women who are currently pregnant or breast-feeding.
• History of interstitial lung disease.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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