A Phase I Study of Methotrexate for HIV Infection

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Patients are randomized to receive methotrexate at Dose 1 or 2 (low doses) for 12 weeks, with 8 weeks of follow-up. If interim safety monitoring and viral burden results for the two cohorts support continuation, a third cohort of patients receive methotrexate starting at Dose 2 for the first 2 weeks, then at Dose 3 for the next 2 weeks, and at Dose 4 for the remaining 8 weeks, with 8 weeks of follow-up.

AS PER AMENDMENT 1/10/97:

The Dose 1 (the lowest dose) has been eliminated; the first 10 patients are now assigned to the next higher dose. Depending upon the results of interim safety data, the next cohort will be entered on the escalating dose regimen.

Also per this amendment, all patients will receive zidovudine and lamivudine for 30 days prior to the initiation of methotrexate, during the 12 weeks of methotrexate administration, and for the 8 weeks of follow-up.

Study Type

Interventional

Enrollment

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Med Ctr
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown Univ Med Ctr
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Univ of Kansas School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • New England Med Ctr
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Harper Hosp
    • New York
      • New York, New York, United States, 10001
        • Community Research Initiative on AIDS
    • Texas
      • Dallas, Texas, United States, 75235
        • Univ of Texas Southwestern Med Ctr of Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Fox L

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

June 1, 2002

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

October 29, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DATRI 013
  • 11742 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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