Ignite Creation Date:
2024-05-05 @ 11:42 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00111397
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2005-05-19
Brief Title:
Adjuvant Cytokine Therapy to Treat Pulmonary Mycobacterium Avium Complex Infection
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Study of Adjuvant Cytokine Therapy in Pulmonary Mycobacterium Avium Complex and Other Pulmonary Nontuberculous Mycobacterial Infections
Status:
COMPLETED
Status Verified Date:
2010-08-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Mycobacterium avium complex MAC are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities Patients typically present with a history of chronic cough eventually progressing to hemoptysis fever and hypoxia With half or more of all patients failing standard three-drug therapy this is an insidious disease with a poor prognosis Under the natural history protocol of nontuberculous mycobacterial infection NTM 01-I-0202 46 patients with diagnosed pulmonary MAC disease are being studied Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection Cytokines are particularly important in the activaction of macrophages which help to clear mycobacterial infection Interferon gamma 1b Actimmune and GM-CSF Leukine are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution respectively A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection Given the poor outcomes of therapy and the persistent debilitating nature of the disease new therapies are desperately needed and many are being tried without benefit of scientific foundation Currently there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously This protocol proposes to perform a pilot study to evaluate the effects if any of these macrophage stimulating cytokines in the context of ongoing pulmonary MAC infection
Aims
To determine the local and systemic effect if any of adjuvant IFN gamma and GM-CSF in pulmonary MAC patients
Methods
Fifteen patients will be randomized into three treatment groups of five patients each The first group will receive a standard drug regimen based on the 1997 ATS guidelines The second and third groups in addition to receiving the standard therapy will also receive three months of IFNgamma and GM-CSF respectively All patients will undergo bronchoscopy with bronchoalveolar lavage BAL at the beginning of the study after three months and at six months
In addition to obtaining traditional subjective and objective clinical measures both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs In vitro studies on typ
Aims
To determine the local and systemic effect if any of adjuvant IFN gamma and GM-CSF in pulmonary MAC patients
Methods
Fifteen patients will be randomized into three treatment groups of five patients each The first group will receive a standard drug regimen based on the 1997 ATS guidelines The second and third groups in addition to receiving the standard therapy will also receive three months of IFNgamma and GM-CSF respectively All patients will undergo bronchoscopy with bronchoalveolar lavage BAL at the beginning of the study after three months and at six months
In addition to obtaining traditional subjective and objective clinical measures both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs In vitro studies on typ
Detailed Description:
Mycobacterium avium complex MAC and other pulmonary nontuberculous mycobacteria P-NTM are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities Patients typically present with a history of chronic cough eventually progressing to hemoptysis fever and hypoxia With half or more of all patients failing standard three-drug therapy this is an insidious disease with a poor prognosis Under the natural history protocol of nontuberculous mycobacterial infection NTM 01-I-0202 46 patients with diagnosed pulmonary MAC disease 20 patients with M abscessus disease and 14 with other types of mycobacteria M fortuitum M massiliense M mucogenicum and M chelonae are being studied
Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection Cytokines are particularly important in the activation of macrophages which help to clear mycobacterial infection Interferon gamma 1b Actimmune and GM-CSF Leukine are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution respectively A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection Given the poor outcomes of therapy and the persistent debilitating nature of the disease new therapies are desperately needed and many are being tried without benefit of scientific foundation Currently there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously This protocol proposes to perform a pilot study to evaluate the effects if any of these macrophage stimulating cytokines in the context of ongoing pulmonary mycobacterial infection
Aims
To determine the local and systemic effect if any of adjuvant IFN gamma and GM-CSF in P-NTM patients
Methods
Fifteen patients will be randomized into three treatment groups of five patients each The first group will receive a standard drug regimen based on the 1997 ATS guidelines The second and third groups in addition to receiving the standard therapy will also receive three months of IFNgamma and GM-CSF respectively All patients will undergo bronchoscopy with bronchoalveolar lavage BAL at the beginning of the study after after three months and at six months
In addition to obtaining traditional subjective and objective clinical measures both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs In vitro studies on type II alveolar macrophages culled from these patients before and after cytokine therapy will also be performed
Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection Cytokines are particularly important in the activation of macrophages which help to clear mycobacterial infection Interferon gamma 1b Actimmune and GM-CSF Leukine are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution respectively A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection Given the poor outcomes of therapy and the persistent debilitating nature of the disease new therapies are desperately needed and many are being tried without benefit of scientific foundation Currently there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously This protocol proposes to perform a pilot study to evaluate the effects if any of these macrophage stimulating cytokines in the context of ongoing pulmonary mycobacterial infection
Aims
To determine the local and systemic effect if any of adjuvant IFN gamma and GM-CSF in P-NTM patients
Methods
Fifteen patients will be randomized into three treatment groups of five patients each The first group will receive a standard drug regimen based on the 1997 ATS guidelines The second and third groups in addition to receiving the standard therapy will also receive three months of IFNgamma and GM-CSF respectively All patients will undergo bronchoscopy with bronchoalveolar lavage BAL at the beginning of the study after after three months and at six months
In addition to obtaining traditional subjective and objective clinical measures both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs In vitro studies on type II alveolar macrophages culled from these patients before and after cytokine therapy will also be performed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-I-0156 | None | None | None |