Interferon Gamma for Drug Resistant Tuberculosis

NCT00001407 | Completed Phase 2

• 2 other identifiers: 94014994-I-0149
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine what dose of recombinant interferon-gamma is safe and effective for treating multiple drug-resistant tuberculosis. Recombinant interferon-gamma is a genetically engineered form of a substance normally produced by the body and is used to boost immune function. Patients 5 years of age and older with multiply drug-resistant tuberculosis may be eligible for this study. Participants will be admitted to either the NIH Clinical Center in Bethesda, Maryland, the Texas Center for Infectious Diseases in San Antonio or the South Texas Hospital or Valley Baptist Hospital, both in Harlingen, Texas. On admission, patients will have a medical history, physical examination, blood and urine tests, sputum culture, X-rays, pulmonary function tests and a computed tomography (CT) scan. CT produces 3-dimensional images of body tissues and organs in small sections. For the procedure, the patient lies still on a table surrounded by the scanner. All patients will continue treatment with anti-tuberculosis antibiotics during and after the study period and may elect whether or not to take gamma interferon in addition to the antibiotic. Five patients will receive only antibiotic treatment, and 5 each will receive one of 3 doses (0.025, 0.05 or 0.1 milligrams per square meter of body surface area) of interferon-gamma injected under the skin 3 times a week. The patient or caregiver will be taught to give the injections, which are similar to insulin injections for diabetes. Patients will be in isolation in the hospital from the start of therapy until sputum samples show no evidence of tuberculosis for 3 consecutive weeks. Following that, they will repeat the tests done on admission (except CT) during follow-up visits (1- to 2-day hospitalizations) at 3, 6, 9, 12, 15, 18 and 24 months after the start of therapy. Patients taking interferon gamma will have blood drawn more frequently (monthly) for the first 6 months, and patients with lung infection will have sputum samples collected more frequently-weekly for the first 3 months or until three consecutive negative samples are obtained and then monthly throughout the course of therapy. Patients with lung infection will also have repeat CT scans at 6 and 12 months while on interferon gamma. In one or two patients on the drug, blood will be drawn frequently following one injection of gamma interferon (just before the injection and again at 0.25, 0.5, 1, 6, 12, 18, 24 and 48 hours after it) to see if a difference in blood levels of the drug can be detected.

Conditions

Pneumonia; Pulmonary Tuberculosis

Keywords

Cytokines; Mycobacteria; Pneumonia; Multiple Drug Resistant Tuberculosis

Interventions

Interferon Gamma DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Presence of causes of secondary immunodeficiency such as HIV or malignancy.
• Currently receiving cytotoxic therapy, or have received it within the last 3 months.
• Pregnant or lactating women may not be entered.
• Patients with a known seizure disorder may not be entered.
• Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery disease may not be entered.
• Patients unable, in the judgment of the PI, to comply with the treatment regimen will be excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Nathan CF, Kaplan G, Levis WR, Nusrat A, Witmer MD, Sherwin SA, Job CK, Horowitz CR, Steinman RM, Cohn ZA. Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy. N Engl J Med. 1986 Jul 3;315(1):6-15. doi: 10.1056/NEJM198607033150102.

  PMID: 3086725 BACKGROUND

• Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993 Sep 9;329(11):784-91. doi: 10.1056/NEJM199309093291108.

  PMID: 8350889 BACKGROUND

• Holland SM, Eisenstein EM, Kuhns DB, Turner ML, Fleisher TA, Strober W, Gallin JI. Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon gamma. A preliminary report. N Engl J Med. 1994 May 12;330(19):1348-55. doi: 10.1056/NEJM199405123301904.

  PMID: 7908719 BACKGROUND

MeSH Terms

Conditions

Pneumonia; Tuberculosis, Pulmonary; Mycobacterium Infections

Interventions

Interferon-gamma

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Tuberculosis; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: May 1, 1994
• Study Completion: May 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-05

Locations

US (1)