Clinical Trials Logo

Clinical Trial 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 (IFN{gamma}) 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...


Clinical Trial 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 (IFN{gamma}) 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 Design


Related Conditions & MeSH terms


NCT number NCT00111397
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase Phase 1
Start date May 13, 2005
Completion date August 4, 2010

See also
  Status Clinical Trial Phase
Completed NCT00000883 - Long-Term Assessment for Metabolic, Cardiovascular and Neurologic Problems in HIV-Infected Patients With Increased CD4 Cells Counts Following Anti-HIV Therapy N/A
Completed NCT00021567 - A Randomized, Double-Blinded, Placebo-Controlled, Phase II Inhaled Interferon Gamma-1b and Antimycobacterials to Treat Pulmonary Mycobacterium Avium Complex Infections Phase 2
Completed NCT00004689 - Phase II Study of Amithiozone (Thiacetazone) for Patients With Mycobacterium Avium Complex Pulmonary Disease Phase 2
Completed NCT00001763 - Subcutaneously Administered Interleukin-12 Therapy in HIV-Infected Patients With Disseminated Mycobacterium Avium Complex Infection Phase 1
Recruiting NCT05824988 - Drug Exposure and Minimum Inhibitory Concentration in the Treatment of MAC Lung Disease
Completed NCT00001047 - Study of Four Different Treatment Approaches for Patients Who Have Mycobacterium Avium Complex Disease (MAC) Plus AIDS Phase 3
Completed NCT00002037 - Evaluation of the Therapeutic Benefit of r-metHuIFN- Gamma in AIDS Patients With Disseminated Mycobacterium Avium-Intracellulare (MAI) Infection: A Multi-Centered Pilot Study N/A
Completed NCT00000947 - A Study to Evaluate the Effects of Azithromycin on MAC Disease Prevention in HIV-Positive Patients N/A
Completed NCT00001058 - A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS Phase 2
Completed NCT00002080 - Rifabutin Therapy for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia in HIV Positive Patients With CD4 Counts = or < 200: Treatment IND Study N/A
Completed NCT00002343 - A Study of Rifabutin, Used Alone or With Ethambutol in the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia in Patients With AIDS Phase 4
Completed NCT00002085 - A Study to Evaluate the Safety and Efficacy of Azithromycin in Individual Patients With Serious Nontuberculous Mycobacterial Disease Who Are Failing or Intolerant of Other Available Therapy N/A
Completed NCT00001995 - A Double-Blind Randomized Clinical Trial of a Rifabutin Regimen in the Treatment of Mycobacterium-Avium Complex (MAC) Bacteremia in Patients With AIDS N/A
Completed NCT00000933 - Effects of MAC Preventive Therapy on Disease-Causing Bacteria in HIV-Infected Patients: A Substudy of CPCRA 048
Completed NCT00002032 - Rifabutin Therapy for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia in AIDS Patients With CD4 Counts = or < 200: A Double-Blind, Placebo-Controlled Trial N/A
Completed NCT00002101 - A Three-Arm Comparative Trial for the Treatment of MAC Bacteremia in AIDS: A Clarithromycin/Ethambutol Regimen Containing Rifabutin (450 Mg) or Rifabutin (300 Mg) or Placebo Phase 3
Completed NCT00000907 - A Study to Examine the Effects of Stopping Preventive Therapy for Disseminated Mycobacterium Avium Complex (DMAC) in HIV-Positive Patients N/A
Completed NCT00002058 - A Randomized Controlled Prophylactic Study of Clofazimine To Prevent Mycobacterium Avium Complex Infection in HIV Disease N/A
Completed NCT00002267 - Rifabutin Therapy for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia in AIDS Patients With CD4 Counts = or < 200: A Double-Blind, Placebo-Controlled Trial N/A
Completed NCT00001023 - The Safety and Effectiveness of Rifabutin, Combined With Clarithromycin or Azithromycin, in HIV-Infected Patients N/A