AIDS-related Complex, Tuberculosis
Conditions
Brief summary
This study will evaluate the lung's immune response to mycobacterium tuberculosis (Mtb) infection and will modulate that response with interferon-gamma.
Detailed description
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.
Interventions
Participants will receive aerosol interferon-gamma.
DRUGSubcutaneous interferon-gamma
Patients will receive subcutaneous interferon-gamma
OTHERPlacebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sputum Conversion | Measured at 16 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Chest Cavity Size | 16 Weeks |
| Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | 16 Weeks |
Countries
South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DOTS Control Group IRPE Anti-Tuberculous Therapy
IRPE Anti-Tuberculous Therapy: Participants will receive IRPE anti-tuberculous therapy. | 30 |
| Aerosol Interferon Gamma for TB Aerosol Interferon-Gamma
Aerosol Interferon-Gamma: Participants will receive aerosol interferon-gamma. | 32 |
| Subcutaneous Interferon Gamma for TB Subcutaneous Interferon-Gamma
Subcutaneous Interferon-Gamma: Participants will receive subcutaneous interferon-gamma. | 27 |
| Total | 89 |
Baseline characteristics
| Characteristic | DOTS Control Group | Aerosol Interferon Gamma for TB | Subcutaneous Interferon Gamma for TB | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 32 Participants | 27 Participants | 89 Participants |
| Age, Continuous | 32 years STANDARD_DEVIATION 11 | 34 years STANDARD_DEVIATION 10 | 35 years STANDARD_DEVIATION 13 | 34 years STANDARD_DEVIATION 10 |
| Gender Female | 10 Participants | 8 Participants | 9 Participants | 27 Participants |
| Gender Male | 20 Participants | 24 Participants | 18 Participants | 62 Participants |
| Region of Enrollment South Africa | 30 participants | 32 participants | 27 participants | 89 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 32 | 0 / 27 |
| serious Total, serious adverse events | 1 / 30 | 3 / 32 | 3 / 27 |
Outcome results
Primary
Sputum Conversion
Time frame: Measured at 16 Weeks
Population: Intention to Treat analysis performed. Only subjects excluded were those who did not receive treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOTS Control Group | Sputum Conversion | 36 percentage of participants |
| Aerosol Interferon Gamma for TB | Sputum Conversion | 60 percentage of participants |
| Subcutaneous Interferon Gamma for TB | Sputum Conversion | 36 percentage of participants |
Secondary
Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels
Time frame: 16 Weeks
Population: Intention to Treat analysis performed. Only subjects excluded were those who did not receive treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DOTS Control Group | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Lymphocytes Week 0 | 4 cells/mL |
| DOTS Control Group | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Lymphocytes Week 16 | 15 cells/mL |
| DOTS Control Group | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Machrophages Week 0 | 60 cells/mL |
| DOTS Control Group | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Machrophages Week 16 | 64 cells/mL |
| DOTS Control Group | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Neutrophils Week 0 | 28 cells/mL |
| DOTS Control Group | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Neutrophils Week 16 | 11 cells/mL |
| Aerosol Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Neutrophils Week 16 | 4 cells/mL |
| Aerosol Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Lymphocytes Week 0 | 5 cells/mL |
| Aerosol Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Machrophages Week 16 | 63 cells/mL |
| Aerosol Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Neutrophils Week 0 | 24 cells/mL |
| Aerosol Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Lymphocytes Week 16 | 15 cells/mL |
| Aerosol Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Machrophages Week 0 | 60 cells/mL |
| Subcutaneous Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Lymphocytes Week 16 | 22 cells/mL |
| Subcutaneous Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Machrophages Week 0 | 62 cells/mL |
| Subcutaneous Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Neutrophils Week 16 | 2 cells/mL |
| Subcutaneous Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Machrophages Week 16 | 66 cells/mL |
| Subcutaneous Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Lymphocytes Week 0 | 6 cells/mL |
| Subcutaneous Interferon Gamma for TB | Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels | Neutrophils Week 0 | 30 cells/mL |
Secondary
Chest Cavity Size
Time frame: 16 Weeks
Population: Intention to Treat analysis performed. Only subjects excluded were those who did not receive treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DOTS Control Group | Chest Cavity Size | Baseline | 34 millimeters | Standard Deviation 11 |
| DOTS Control Group | Chest Cavity Size | 16 Weeks | 20 millimeters | Standard Deviation 16 |
| Aerosol Interferon Gamma for TB | Chest Cavity Size | Baseline | 39 millimeters | Standard Deviation 24 |
| Aerosol Interferon Gamma for TB | Chest Cavity Size | 16 Weeks | 29 millimeters | Standard Deviation 24 |
| Subcutaneous Interferon Gamma for TB | Chest Cavity Size | Baseline | 34 millimeters | Standard Deviation 13 |
| Subcutaneous Interferon Gamma for TB | Chest Cavity Size | 16 Weeks | 18 millimeters | Standard Deviation 17 |