A Phase I Study of Methotrexate for HIV Infection

• Status: Completed
• Trial end date: 2002-06-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the safety and tolerance of methotrexate in HIV-infected patients. To determine the dose effective in modulating key markers of immune activation. To determine a dose suitable for Phase II or III evaluation in HIV-infected patients.

In HIV infection, complete immunological clearance of the foreign antigen does not occur, resulting in chronic immune activation. Because chronic immune activation may contribute to disease progression in HIV infection, immunomodulators may have therapeutic value in early HIV disease prior to development of opportunistic infections. The clinical benefits of methotrexate appear to derive from an anti-inflammatory effect; thus, it may reduce the state of chronic immune activation.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Lamivudine; Methotrexate; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiemetics and antidiarrheals.

• Acetaminophen.

• Oral hypoglycemic agents.

PER AMENDMENT 5/15/96:

• Stable dose of antiretroviral (must be stable for at least 1 month prior to study entry). [AS

PER AMENDMENT 1/10/97:

• Combination zidovudine/lamivudine or zidovudine alone.]

Patients must have:

• HIV seropositivity.

• CD4 count >= 300 cells/mm3.

• No AIDS-defining condition.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptom or condition are excluded:

• Current positive PPD.

Concurrent Medication:

Excluded:

• Immunosuppressive or immunomodulatory drugs.

• Chronic nonsteroidal anti-inflammatory agents.

• Newly initiated antiretrovirals.

• Bone marrow suppressive drugs (e.g., TMP/SMX).

Concurrent Treatment:

AS PER AMENDMENT 1/10/97: Excluded:

• Antiretroviral therapy other than combination zidovudine/lamivudine or zidovudine alone; no initiation of other antiretroviral therapy should be planned while patient is on methotrexate.

Patients with the following prior conditions are excluded:

• Prior malignancies.

• Prior mucocutaneous herpes infection requiring antiviral therapy [AS PER AMENDMENT 7/31/96: Prior mucocutaneous herpes infection requiring systemic treatment with an antiviral agent (e.g., acyclovir); history of topical antiviral therapy is permitted].

• Anergic on DTH skin test within the past month (PER AMENDMENT 5/15/96: patients who are positive on DTH skin test but unable to receive the HIV-1 skin test because of allergies to insects, bee stings, etc., remain eligible for study enrollment).

• Inflammatory bowel disease, peptic ulcer disease, obesity combined with insulin-requiring diabetes, liver disease, or chronic renal disease within the past 6 months.

• Positive for HBsAg or hepatitis C antibody within the past 2 weeks.

• Chest radiograph within the past 60 days that shows cavity disease, infiltrates, or scars from prior disease that would preclude diagnosis of a new infectious process or drug-induced pneumonitis.

AS PER AMENDMENT 1/10/97:

• History of intolerance to zidovudine or lamivudine.

Prior Medication:

Excluded:

• Prior chemotherapy for malignancy.

Prior Treatment:

Excluded:

• Prior radiotherapy for malignancy. Alcohol abuse.