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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00201123
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 89
• Locations: 2
• Arms: 3
• Duration (Months): 28
• Patients Per Site: 44.5
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis; AIDS-related Complex	Drug: Aerosol Interferon-Gamma; Drug: Subcutaneous interferon-gamma; Other: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Host Response to Tuberculosis and Acquired Immune Deficiency Syndrome
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Aug 1, 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Sputum Conversion [Measured at 16 Weeks]

Secondary Outcome Measures

1. Chest Cavity Size [16 Weeks]

2. Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels [16 Weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU School of Medicine	New York	New York	United States	10016
2	The Lung Institute at University of Cape Town	Cape Town		South Africa

Sponsors and Collaborators

• NYU Langone Health
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: William Rom, MD, MPH, NYU School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00201123
• Other Study ID Numbers: 264; R01HL059832-06
• First Posted: Sep 20, 2005
• Last Update Posted: Dec 16, 2016
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Tuberculosis; AIDS-Related Complex; Interferons; Interferon-gamma

Study Results

Participant Flow

Arm/Group Title	DOTS Control Group	Aerosol Interferon Gamma for TB	Subcutaneous Interferon Gamma for TB
Arm/Group Description	DOTS Control Group IRPE Anti-Tuberculous Therapy: Participants will receive IRPE anti-tuberculous therapy.	Aerosol Interferon-Gamma Aerosol Interferon-Gamma: Participants will receive aerosol interferon-gamma.	Subcutaneous Interferon-Gamma Subcutaneous Interferon-Gamma: Partcipants will receive subcutaneous interferon-gamma.
Period Title: Overall Study
STARTED	32	32	32
Did Not Meet Continuation Criteria	2	0	5
COMPLETED	26	28	23
NOT COMPLETED	6	4	9

Baseline Characteristics

Arm/Group Title	DOTS Control Group	Aerosol Interferon Gamma for TB	Subcutaneous Interferon Gamma for TB	Total
Arm/Group Description	IRPE Anti-Tuberculous Therapy IRPE Anti-Tuberculous Therapy: Participants will receive IRPE anti-tuberculous therapy.	Aerosol Interferon-Gamma Aerosol Interferon-Gamma: Participants will receive aerosol interferon-gamma.	Subcutaneous Interferon-Gamma Subcutaneous Interferon-Gamma: Participants will receive subcutaneous interferon-gamma.	Total of all reporting groups
Overall Participants	30	32	27	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (11)	34 (10)	35 (13)	34 (10)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	30 100%	32 100%	27 100%	89 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Gender (Count of Participants)
Female	10 33.3%	8 25%	9 33.3%	27 30.3%
Male	20 66.7%	24 75%	18 66.7%	62 69.7%
Region of Enrollment (participants) [Number]
South Africa	30 100%	32 100%	27 100%	89 100%

Outcome Measures

1. Primary Outcome

Title	Sputum Conversion
Time Frame	Measured at 16 Weeks

Outcome Measure Data

Analysis Population Description

Intention to Treat analysis performed. Only subjects excluded were those who did not receive treatment.

Arm/Group Title	DOTS Control Group	Aerosol Interferon Gamma for TB	Subcutaneous Interferon Gamma for TB
Arm/Group Description	IRPE Anti-Tuberculous Therapy IRPE Anti-Tuberculous Therapy: Participants will receive IRPE anti-tuberculous therapy.	Aerosol Interferon-Gamma Aerosol Interferon-Gamma: Participants will receive aerosol interferon-gamma.	Subcutaneous Interferon-Gamma Subcutaneous Interferon-Gamma: Partcipants will receive subcutaneous interferon-gamma.
Measure Participants	30	32	27
Number [percentage of participants]	36 120%	60 187.5%	36 133.3%

2. Secondary Outcome

Title	Chest Cavity Size
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Intention to Treat analysis performed. Only subjects excluded were those who did not receive treatment.

Arm/Group Title	DOTS Control Group	Aerosol Interferon Gamma for TB	Subcutaneous Interferon Gamma for TB
Arm/Group Description	IRPE Anti-Tuberculous Therapy IRPE Anti-Tuberculous Therapy: Participants will receive IRPE anti-tuberculous therapy.	Aerosol Interferon-Gamma Aerosol Interferon-Gamma: Participants will receive aerosol interferon-gamma.	Subcutaneous Interferon-Gamma Subcutaneous Interferon-Gamma: Participants will receive subcutaneous interferon-gamma.
Measure Participants	32	30	27
Baseline	34 (11)	39 (24)	34 (13)
16 Weeks	20 (16)	29 (24)	18 (17)

3. Secondary Outcome

Title	Bronchoalveolar Lavage (BAL) to Measure Flow of Cytometry and Cytokine Levels
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Intention to Treat analysis performed. Only subjects excluded were those who did not receive treatment.

Arm/Group Title	DOTS	Nebulized rlFN-y	Subcutaneous rlFN-y
Arm/Group Description
Measure Participants	30	32	27
Lymphocytes Week 0	4	5	6
Lymphocytes Week 16	15	15	22
Machrophages Week 0	60	60	62
Machrophages Week 16	64	63	66
Neutrophils Week 0	28	24	30
Neutrophils Week 16	11	4	2

Adverse Events

Arm/Group Title	DOTS Control Group		Aerosol Interferon Gamma for TB		Subcutaneous Interferon Gamma for TB
Arm/Group Description	DOTS Control Group IRPE Anti-Tuberculous Therapy: Participants will receive IRPE anti-tuberculous therapy.		Aerosol Interferon-Gamma Aerosol Interferon-Gamma: Participants will receive aerosol interferon-gamma.		Subcutaneous Interferon-Gamma Subcutaneous Interferon-Gamma: Partcipants will receive subcutaneous interferon-gamma.
All Cause Mortality
	DOTS Control Group		Aerosol Interferon Gamma for TB		Subcutaneous Interferon Gamma for TB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	DOTS Control Group		Aerosol Interferon Gamma for TB		Subcutaneous Interferon Gamma for TB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		3/32 (9.4%)		3/27 (11.1%)
Respiratory, thoracic and mediastinal disorders
hemoptysis	1/30 (3.3%)		0/32 (0%)		0/27 (0%)
Desaturation on BAL	0/30 (0%)		2/32 (6.3%)		2/27 (7.4%)
pneumonia	0/30 (0%)		1/32 (3.1%)		1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	DOTS Control Group		Aerosol Interferon Gamma for TB		Subcutaneous Interferon Gamma for TB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/32 (0%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.