Effects of Interferon-Gamma on Cavitary Pulmonary Tuberculosis in the Lungs

Study Overview
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Brief Summary
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This study will evaluate the lung's immune response to mycobacterium tuberculosis (Mtb) infection and will modulate that response with interferon-gamma.

Detailed Description
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BACKGROUND: Mtb infects one-third of the world's population and ranks seventh in terms of global morbidity and mortality. Patients with bilateral pulmonary tuberculosis (TB), cavitary disease, and persistently positive sputum smears pose a special risk for treatment failure and/or relapse. DESIGN NARRATIVE: Cavitary pulmonary TB will be studied and interferon-gamma will be used as the intervention. The outcome of this study will be the changes in mycobacteriology, chest radiography, and bronchoalveolar lavage (BAL) cells. The primary outcome will be sputum conversion, which will be measured at Weeks 4 and 8. The key secondary outcomes of this study will include a chest computerized tomography (CT) scan and BAL to measure the flow of cytometry and cytokine levels. Both outcomes will be measured at baseline and at Month 4.

Official Title
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Host Response to Tuberculosis and Acquired Immune Deficiency Syndrome

Conditions
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Tuberculosis, AIDS-related Complex

Intervention / Treatment
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* Drug: Aerosol Interferon-Gamma
* Drug: Subcutaneous interferon-gamma
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive acid-fast bacillus (AFB) smear within 14 days prior to randomization Cluster of Differentiation 4 greater than 200 if HIV positive Ability to sign consent Bilateral, cavitary pulmonary TB Exclusion Criteria: Multidrug-resistant (MDR) TB Extrapulmonary TB HIV positive with opportunistic infection within 30 days of study entry Cancer Asthma Pregnant or lactating women Chronic heart disease Chronic liver disease Chronic renal disease Seizure disorder Bleeding or clotting disorder Diabetes mellitus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard Treatment<br>Isoniazid, Rifampin, Pyrazinamide Anti-Tuberculous Therapy | Other: Placebo<br> <br> |
| Experimental: Aerosol Interferon-gamma<br>Aerosol Interferon-Gamma plus Isoniazid, Rifampin, and Pyrazinamide | Drug: Aerosol Interferon-Gamma<br>* Participants will receive aerosol interferon-gamma.<br>|
| Experimental: Subcutaneous Interferon-Gamma<br>Subcutaneous Interferon-Gamma plus Isoniazid, Rifampin, and Pyrazinamide | Drug: Subcutaneous interferon-gamma<br>* Patients will receive subcutaneous interferon-gamma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum Conversion |  | Measured at 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest Cavity Size |  | 16 Weeks | 
| Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels |  | 16 Weeks |