Adjuvant Cytokine Therapy to Treat Pulmonary Mycobacterium Avium Complex Infection
Status:
Completed
Trial end date:
2010-08-04
Target enrollment:
Participant gender:
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...
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)