A Phase I Study of Methotrexate for HIV Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000834
First received: November 2, 1999
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Lamivudine
Drug: Methotrexate
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Phase I Study of Methotrexate for HIV Infection

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 30
Study Completion Date: June 2002
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000834

Locations
United States, California
Cedars Sinai Med Ctr
Los Angeles, California, United States, 90048
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
United States, Kansas
Univ of Kansas School of Medicine
Wichita, Kansas, United States, 67214
United States, Massachusetts
New England Med Ctr
Boston, Massachusetts, United States, 02111
United States, Michigan
Harper Hosp
Detroit, Michigan, United States, 48201
United States, New York
Community Research Initiative on AIDS
New York, New York, United States, 10001
United States, Texas
Univ of Texas Southwestern Med Ctr of Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Investigators
Study Chair: Egorin M
Study Chair: Fox L
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000834     History of Changes
Other Study ID Numbers: DATRI 013, 11742
Study First Received: November 2, 1999
Last Updated: May 23, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Methotrexate
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lamivudine
Disease Progression
Anti-Inflammatory Agents
Anti-HIV Agents

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Methotrexate
Lamivudine
Zidovudine
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 18, 2014