Study of Mycobacterial Infections

This study is currently recruiting participants.
Verified August 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00018044
First received: June 28, 2001
Last updated: March 14, 2014
Last verified: August 2013
  Purpose

This study will examine the symptoms, course of disease and treatment of non-tuberculous mycobacterial (NTM) infections, as well as the genetics involved in these infections. Patients with NTM have recurrent lung infections and sometimes infections of the skin and other organs as well. They may also have curvature of the spine, barrel chest, and heart valve weakness. The study will compare the features of NTM with those of Job syndrome and cystic fibrosis, other diseases involving recurrent infections of the lungs and possibly other organs.

Patients with diagnosed or suspected non-tuberculous mycobacterial infection, cystic fibrosis or Job syndrome may be eligible for this study. All participants will have a medical and family history, blood and urine tests, imaging studies that may include X-rays, computed tomography (CT) or magnetic resonance imaging (MRI) scans, and DNA and other genetic studies. In addition, all patients with Job syndrome and cystic fibrosis, and patients with NTM who have lung disease undergo the following procedures:

  • Scoliosis survey X-rays of the spine to look for curvature or other abnormalities of the spinal column
  • Echocardiography imaging test that uses sound waves to examine the heart chambers and valves
  • Electrocardiogram measurement of the electrical activity of the heart
  • Pulmonary function tests breathing tests to measure how much air the patient can move into and out of the lungs
  • Body measurements measurements of height, weight, arm span, finger length, etc.
  • Joint function assessment of joint mobility using different maneuvers to test flexibility of joints and ligaments
  • Examination of physical features that might be associated with NTM, such as high arched palate of the mouth, flat feet, or certain skin features
  • Dermatology (skin) examination for reactive skin conditions or other skin problems and possibly a skin biopsy (surgical removal of a small skin tissue sample for microscopic examination)
  • Interview with genetics specialist

These tests may require several days to complete. Patients with NTM will also be examined by a cystic fibrosis specialist and may have a sweat test. In addition, NTM patients will be asked to return to NIH every year for 5 years for follow-up tests, if medically indicated, including CT of the chest, scoliosis survey and examination by other specialists.


Condition
Atypical Mycobacterium Infections
Cystic Fibrosis
Job's Syndrome

Study Type: Observational
Official Title: Natural History, Genetics, Phenotype and Treatment of Mycobacterial Infections

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 700
Study Start Date: June 2001
Detailed Description:

The nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms found in soil and water that rarely cause disease in humans. Since exposure to these organisms is universal and disease is rare, it can be concluded that normal host defenses are sufficient to prevent infection. It follows that otherwise healthy individuals that develop disease may have abnormal susceptibility or immune defects that permit infection with nontuberculous mycobacteria. The organisms that are most commonly encountered in clinical practice include Mycobacterium avium, and M. intracellulare [collectively known as the M. avium complex (MAC)], M. kansasii, M. fortuitum, M. abscessus, and M. chelonae. These organisms share significant structural and biochemical similarities with their more pathogenic relative, M. tuberculosis (MTB). Recognition of host factors that predispose or lead to NTM infection may have important implications for pathogenesis and therapeutic intervention, and may be applicable to the more virulent MTB. Identification of genetic or acquired susceptibility factors may lead to recognition of endogenous pathways that can be exploited therapeutically and to possible gene identification.

Over the last two decades, three important observations have been made regarding the pathogenesis of nontuberculous mycobacterial infections. 1) In patients infected with HIV, nontuberculous mycobacterial infections often occur when the CD4+ T-lymphocyte number falls below 50/mm(3). This suggested that specific T cell products or activities were required for mycobacterial resistance. 2) An association was noted between pulmonary nontuberculous mycobacterial infections and a particular body habitus, predominantly in post-menopausal women (pectus excavatum, scoliosis, mitral valve prolapse). 3) Multiple defects have been found involving the interferon gamma synthesis and use pathways in patients with disseminated nontuberculous mycobacterial infection without HIV, suggesting this is a critical pathway for host defense against these organisms.

We seek to better characterize the predisposition to mycobacterial infection. This study will specifically address several aspects of immune function and investigate the proposed link to body morphotype in the relevant population. By collecting this information, we hope to provide insight into disease associations, infection susceptibility, and genetic predisposition to mycobacterial infection.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA FOR PATIENTS:

This protocol will study patients with mycobacterial infections, including those without previously identified predisposing disease processes as well as individuals with underlying malignancies.

Patients with nontuberculous mycobacterial infections will be of particular interest, as we are interested in isolating and characterizing the primary immune defect(s) responsible for this infection susceptibility.

Select patients with acquired immunodeficiencies or tuberculosis may also be studied if relevant host defects are suspected.

Patients must be referred to NIH with a diagnosis or suspicion of having mycobacterial infection.

Male and female patients will be accepted without limitations due to age.

Only patients with nontuberculous mycobacterial infections without HIV infection will be considered for long-term disease management.

INCLUSION CRITERIA FOR RELATIVES:

As part of this protocol, we may obtain medical records, family member questionnaire, blood work, urine, saliva or buccal swab from some blood relatives of patients on the study, with the hope of isolating and characterizing the primary immune defect(s) responsible for mycobacterial infection susceptibilityand if there are any genetic links seen within families. We hope to identify families with an apparent genetic susceptibility to respiratory diseases predominantly associated with P-NTM and perform whole genome sequencing within this group to identify genetic mutations accounting for this increased susceptibility. Male and female patients will be accepted without limitation due to age. These relatives will not receive treatment or have any other protocol procedures done unless they become a patient on the study.

EXCLUSION CRITERIA:

None.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00018044

Contacts
Contact: Reginald J Claypool, R.N. (301) 402-7831 rclaypool@niaid.nih.gov
Contact: Steven M Holland, M.D. (301) 402-7684 sholland@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Steven M Holland, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00018044     History of Changes
Other Study ID Numbers: 010202, 01-I-0202
Study First Received: June 28, 2001
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Morphotype
Pulmonary
Infection
Mycobacterium
Nontuberculous
Mycobacterial Infection
Nontuberculous Mycobacterial Infection
NTM
Job's Syndrome
Job Syndrome
Cystic Fibrosis
CF

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Job's Syndrome
Mycobacterium Infections
Mycobacterium Infections, Atypical
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on April 15, 2014