A Study of Tumor Necrosis Factor and Human Interferon-gamma in Patients With AIDS Related Complex

NCT ID: NCT00001004

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1990-02-28

Brief Summary

To study the tolerance and toxicity of the combination of tumor necrosis factor (TNF) and interferon gamma (IFN-G) or as single agent TNF or IFN-G in HIV infected patients. To selectively monitor the immune system of AIDS related complex (ARC) patients who receive either combination therapy or TNF or IFN-G alone. To obtain information on the effectiveness of combination therapy or TNF or IFN-G alone against HIV in ARC patients.

Recombinant TNF and recombinant IFN-G have been shown to be effective against the virus which causes AIDS and ARC in some laboratory studies, but may increase virus replication in other laboratory studies. Previous studies in humans showed no increase in virus cultures and some decrease in measurements of virus. Extensive preclinical data show that TNF and IFN-G are more effective together than separately in laboratory and animal studies. As single agents, both TNF and IFN-G have modest effect against HIV. Studies have demonstrated that TNF and IFN-G, in combination, can not only inhibit HIV infection of previously uninfected cells, but also can selectively induce the destruction of acutely infected target cells.

Detailed Description

Recombinant TNF and recombinant IFN-G have been shown to be effective against the virus which causes AIDS and ARC in some laboratory studies, but may increase virus replication in other laboratory studies. Previous studies in humans showed no increase in virus cultures and some decrease in measurements of virus. Extensive preclinical data show that TNF and IFN-G are more effective together than separately in laboratory and animal studies. As single agents, both TNF and IFN-G have modest effect against HIV. Studies have demonstrated that TNF and IFN-G, in combination, can not only inhibit HIV infection of previously uninfected cells, but also can selectively induce the destruction of acutely infected target cells.

Patients with ARC who are positive for HIV antibody are randomized to receive one of three treatment arms: (1) TNF alone by intramuscular injection (IM); (2) IFN-G alone by IM; (3) TNF plus IFN-G. Patients receive IM injections 3 times weekly for 4 months (16 weeks). Repeated physical examinations and laboratory tests are used to monitor patients' safety. Serial HIV cultures and core antigen assays are employed to obtain evidence of antiviral activity and serial T cell and skin tests are used to measure immunologic effect.

Conditions

HIV Infections

Keywords

Tumor Necrosis Factor; Interferon-gamma, Recombinant; HIV Antigens; Immunologic Surveillance; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Tumor Necrosis Factor

Intervention Type: DRUG

Interferon gamma-1b

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Patients who have a primary diagnosis of AIDS related complex (ARC) including lymphadenopathy syndrome (LAS), who are positive for HIV antibody, have a minimum life expectancy of 3 months, and have one or more of the following symptoms for = or > 30 days:

• Fever.
• Night sweats.
• Fatigue.
• Oral thrush.
• Hairy leukoplakia.
• Diarrhea.
• Weight loss < 10 percent.
• Patients must be able to sign a written informed consent form, which must be obtained prior to treatment.

Concurrent Medication:

Allowed:

• Acetaminophen for temperature rise of > 38.5 degrees C - 650 mg by mouth every 4 hours on an as needed basis.

Severe rigors may be treated (or prevented) with meperidine 50 mg IV on an as needed basis in the absence of systolic hypotension < 80 mm Hg.

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Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Clinically significant cardiac disease - New York Heart Association Class II, III, or IV.
• Hemorrhagic diathesis (including hemophilia) or active bleeding disorder (e.g., genitourinary, gastrointestinal).
• Clinically apparent vascular disease (including a prior history of pulmonary embolus, deep venous thrombosis, or peripheral arterial occlusive disease).

Concurrent Medication:

Excluded:

• Medications required for the treatment of active cardiac disease including cardiac glycosides, antiarrhythmics and antianginal agents.
• Anticoagulants.
• Thrombolytic agents.
• Nonsteroidal anti-inflammatory drugs.
• Ongoing therapy with vasodilators.
• Aspirin.
• Corticosteroids.
• Antihistamines.
• Barbiturates.
• Excluded within 4 weeks of study entry:
• Antiviral chemotherapy.
• Immunotherapy.
• Excluded within 12 weeks of study entry:
• Suramin.

Patients with the following are excluded:

• AIDS-associated opportunistic infection.
• Lipoprotein disorders.
• Hemophilia.

Prior Medication:

Excluded:

• Interferon gamma.
• Tumor necrosis factor.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kaplan L

Role: STUDY_CHAIR

Corey L

Role: STUDY_CHAIR

Locations

Univ of Washington

Seattle, Washington, United States

Countries

United States

References

Agosti JM, Coombs R, Kidd PG, Paradise M, Sherwin S, Corey L. Randomized phase II trial of recombinant tumor necrosis factor (rTNF) and recombinant interferon-gamma (rIFN-gamma) in patients with ARC. Int Conf AIDS. 1989 Jun 4-9;5:558 (abstract no MCP101)

Reference Type: BACKGROUND

Agosti JM, Coombs RW, Collier AC, Paradise MA, Benedetti JK, Jaffe HS, Corey L. A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group). AIDS Res Hum Retroviruses. 1992 May;8(5):581-7. doi: 10.1089/aid.1992.8.581.

Reference Type: BACKGROUND

PMID: 1515211 (View on PubMed)

Other Identifiers

11001

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 025

Identifier Type: -

Identifier Source: org_study_id