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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tumor Necrosis Factor
Interferon gamma-1b
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Tumor Necrosis Factor, Interferon-gamma, Recombinant, HIV Antigens, Immunologic Surveillance, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. - 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.

Sites / Locations

  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001004
Brief Title
A Study of Tumor Necrosis Factor and Human Interferon-gamma in Patients With AIDS Related Complex
Official Title
A Randomized Multicenter Phase II Trial of Recombinant Tumor Necrosis Factor and Recombinant Human Interferon-gamma in Patients With AIDS Related Complex
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 1990 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Tumor Necrosis Factor, Interferon-gamma, Recombinant, HIV Antigens, Immunologic Surveillance, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
Double
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Tumor Necrosis Factor
Intervention Type
Drug
Intervention Name(s)
Interferon gamma-1b

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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. - 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kaplan L
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Corey L
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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)
Results Reference
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PubMed Identifier
1515211
Citation
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.
Results Reference
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A Study of Tumor Necrosis Factor and Human Interferon-gamma in Patients With AIDS Related Complex

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