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The Safety and Effectiveness of Injections of Human Recombinant Interferon-gamma in Patients With AIDS Who Have Taken Zidovudine

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
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 Monocytes, Interferon-gamma, Recombinant, Injections, Subcutaneous, Immune System, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, Blood Bactericidal Activity

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Prophylactic antibiotics. Tylenol (650 mg orally every 6 hours as needed for temperature > 38.5 degrees C). Meperidine (25 - 50 mg intravenously, once, for severe rigors if systolic blood pressure is > 90 mmHg). Patients must meet criteria for AIDS classification (CDC) category IV C-1. Patients must have had one or more prior opportunistic infections identified in surveillance definition of AIDS. Patients whose AIDS-defining illness is Kaposi's sarcoma are also eligible if they have previously had one of the secondary infectious diseases identified in category C-1. Prior Medication: Required: Patients must have been receiving zidovudine (AZT) on a stable dosage regimen for at least 8 weeks immediately preceding entry into study. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment. Presence of an active opportunistic infection that requires treatment. Hemorrhagic diathesis or active bleeding disorder. Clinically apparent vascular disease. Concurrent Medication: Excluded: Medications required for treatment of active cardiac disease. Ongoing therapy with anticoagulants or thrombolytic agents. Patients with the following are excluded: Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment. Presence of an active opportunistic infection that requires treatment. Hemorrhagic diathesis or active bleeding disorder. Clinically apparent vascular disease. Prior Medication: Excluded within 4 weeks of study entry: Antiviral chemotherapy other than zidovudine. Excluded within 12 weeks of study entry: Immunosuppressive or cytotoxic therapy.

Sites / Locations

  • Cornell University A2201

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
NCT00001112
Brief Title
The Safety and Effectiveness of Injections of Human Recombinant Interferon-gamma in Patients With AIDS Who Have Taken Zidovudine
Official Title
A Phase I Study To Determine the Safety of the Optimal Monocyte Activating Administration Schedule of Subcutaneous Human Recombinant Interferon-gamma in ZDV-Treated Patients With AIDS
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
April 1993 (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 find out which of four doses of (recombinant) human interferon gamma (IFN-G) is most effective in stimulating the white blood cells (monocytes) to fight infection and to see if treatment with IFN-G can strengthen the ability of AIDS patients to control infections. This study will also determine how long after a single injection of IFN-G white blood cells remain stimulated. AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best.
Detailed Description
AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best. Patients, who may participate in all three parts of the study, are maintained on a stable dose of AZT. In part A (optimal dose), five AIDS patients who have had an AIDS related opportunistic infection receive 4 once-weekly increasing doses of IFN-G. Monocyte antimicrobial activity is examined in test tube studies before and after each injection of IFN-G. In part B, five patients receive the optimal dose of IFN-G established in part A. Patients enrolled from part A have completed at least 2 weeks of part A before enrolling in part B. Antimicrobial activity is examined 1, 2, and 3 days after a single injection of the optimal dose of IFN-G (determined in part A). In part C (safety and tolerance of combined treatment of IFN-G and AZT), patients are treated with IFN-G for 4 weeks using the optimal dose and administration schedule derived from parts A and B.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Monocytes, Interferon-gamma, Recombinant, Injections, Subcutaneous, Immune System, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, Blood Bactericidal Activity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
5 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine
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
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Prophylactic antibiotics. Tylenol (650 mg orally every 6 hours as needed for temperature > 38.5 degrees C). Meperidine (25 - 50 mg intravenously, once, for severe rigors if systolic blood pressure is > 90 mmHg). Patients must meet criteria for AIDS classification (CDC) category IV C-1. Patients must have had one or more prior opportunistic infections identified in surveillance definition of AIDS. Patients whose AIDS-defining illness is Kaposi's sarcoma are also eligible if they have previously had one of the secondary infectious diseases identified in category C-1. Prior Medication: Required: Patients must have been receiving zidovudine (AZT) on a stable dosage regimen for at least 8 weeks immediately preceding entry into study. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment. Presence of an active opportunistic infection that requires treatment. Hemorrhagic diathesis or active bleeding disorder. Clinically apparent vascular disease. Concurrent Medication: Excluded: Medications required for treatment of active cardiac disease. Ongoing therapy with anticoagulants or thrombolytic agents. Patients with the following are excluded: Clinically significant cardiac (= or > class II, New York Heart Association) or peripheral vascular disease that requires treatment. Presence of an active opportunistic infection that requires treatment. Hemorrhagic diathesis or active bleeding disorder. Clinically apparent vascular disease. Prior Medication: Excluded within 4 weeks of study entry: Antiviral chemotherapy other than zidovudine. Excluded within 12 weeks of study entry: Immunosuppressive or cytotoxic therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
HW Murray
Official's Role
Study Chair
Facility Information:
Facility Name
Cornell University A2201
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
3104467
Citation
Murray HW, Scavuzzo D, Jacobs JL, Kaplan MH, Libby DM, Schindler J, Roberts RB. In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes. J Immunol. 1987 Apr 15;138(8):2457-62.
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The Safety and Effectiveness of Injections of Human Recombinant Interferon-gamma in Patients With AIDS Who Have Taken Zidovudine

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