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The Role of Inflammasome in Inflammatory Macrophage in Mycobacterium Avium Complex-lung Disease and Mycobacterium Abscessus-lung Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT02005094
First received: November 26, 2013
Last updated: June 27, 2014
Last verified: June 2014
  Purpose
  1. To investigate the inflammasome response of inflammatory and resting macrophage derived from healthy human participants by stimulation using MAC or MAB bacilli.
  2. To compare the difference of inflammasome response of inflammatory macrophage by MAC/MAB bacilli stimulation between MAC/MAB-LD patients and the colonizers.
  3. To study the diagnostic aid from immunological markers in inflammasome response in inflammatory macrophage stimulated by MAC/MAB.

Condition
To Investigate the Inflammasome Response of Inflammatory and Resting Macrophage
To Compare the Difference of Inflammasome Response of Inflammatory Macrophage
To Study the Diagnostic Aid From Immunological Markers in Inflammasome Response

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Role of Inflammasome in Inflammatory Macrophage in Mycobacterium Avium Complex-lung Disease and Mycobacterium Abscessus-lung Disease

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • survival [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • the amount of cytokine released by inflammatory macrophage [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: November 2013
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Healthy group
patients without MAC/MAB lung disease and colonization
MAC/MAB colonization group
patients with pulmonary MAC/MAB colonization
MAC/MAB lung disease group
Patient with MAC/MAB lung disease

Detailed Description:

Lung disease (LD) due to nontuberculous mycobacteria (NTM) becomes an important clinical concern, because the incidence and prevalence of NTM-LD have increased over the last decade. Among the NTM-LD in Taiwan, Mycobacterium avium complex (MAC) and M. abscessus (MAB) are the most frequent pathogenic species. Because MAC and MAB exist in the environment ubiquitously, clinical relevance of MAC isolated in sputum is only around 35~42%, and that of MAB is around 33%. According to the guideline of the American Thoracic Society, the diagnosis of MAC-LD and MAB-LD is based on clinical, radiographic, and mycobacteriologic criteria. For microbiology criteria, two or more sets of positive sputum mycobacterial culture for the same NTM species within one year is required. Actually, mycobacteria culture is neither timely nor efficient, which needs weeks to wait the results, especially for the slowly growing NTM. Moreover, the nucleic acid amplification method cannot discriminate true NTM infection and solely colonization because airway NTM colonization is not uncommon. Therefore, diagnosis of true NTM-LD is a big challenge in clinical practice. However, to early diagnose and then start treatment of NTM-LD is important because NTM-LD may be rapid lethal in critical status or in patients without early proper treatment. Hence, more rapid and accurate diagnostic test should be developed.

The body inflammatory markers are probably indicators for differentiating true NTM-LD from pulmonary colonization and interferon-gamma (IFN-g) play a critical role in protective immunity to mycobacterial infections. However, serum IFN-g poorly correlated with diagnosis of NTM-LD and possibly due to the hosts with attenuated cellular immunity and the presence of IFN-gamma inhibitor. By contrast, macrophages are the first-line defense while mycobacterial bacilli enter through airway and may play an important role while MAC/MAB infection. Macrophages can be polarized to inflammatory type and promotes type 1 immunity. In addition, inflammatory macrophages can react through inflammasome to defense intracellular mycobacteria. However, the inflammasome responses in inflammatory macrophages are rarely investigated in MAC-LD and MAB-LD, either for the defense mechanism or its diagnostic aid for disease form colonization. The investigators therefore conduct an in-vitro inflammatory macrophage stimulation using MAC or MAB bacilli to observe the difference of inflammasome response between MAC/MAB patients, colonizers, and controls.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
  1. Age ≥ 20 years
  2. MAC/MAB lung disease: Diagnosis is based on the guidelines made by American Thoracic Society (Table 1)[1]. In brief, there should be pulmonary symptoms, comparable findings in chest image and appropriate exclusion other possible causes as well as meeting the microbiology criteria.
  3. MAC/MAB pulmonary colonizers: Those without fulfilling the diagnostic criteria but having at least one set of positive sputum for MAC/MAB are defined.
  4. Healthy controls: patient without documented MAC/MAB lung disease and pulmonary colonization
Criteria

Inclusion Criteria:

  • Age ≥ 20 years
  • MAC/MAB lung disease: Diagnosis is based on the guidelines made by American Thoracic Society (Table 1)[1]. In brief, there should be pulmonary symptoms, comparable findings in chest image and appropriate exclusion other possible causes as well as meeting the microbiology criteria.
  • MAC/MAB pulmonary colonizers: Those without fulfilling the diagnostic criteria but having at least one set of positive sputum for MAC/MAB are defined.
  • Healthy controls: patient without documented MAC/MAB lung disease and pulmonary colonization

Exclusion Criteria:

  • Patients who have acquired immunodeficiency syndrome
  • Patients who have bleeding tendency which cannot tolerate venous puncture such as hemophilia, thrombocytopenia.
  • refusal of recruitment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02005094

Contacts
Contact: Chin-Chung Shu, MD 886-972653087 stree139@yahoo.com.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Chin-CHung Shu, MD    886-972653087      
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Chin-Chung Shu, MD National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02005094     History of Changes
Other Study ID Numbers: 201308008RINA
Study First Received: November 26, 2013
Last Updated: June 27, 2014
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Lung Diseases
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections, Nontuberculous
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 24, 2014