ClinicalTrials.gov
ClinicalTrials.gov Menu

Biologic Basis Of Increased Susceptibility Of Smokers To Pulmonary Infection With Mycobacterium Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02021747
Recruitment Status : Withdrawn (Research Changed Directions)
First Posted : December 27, 2013
Last Update Posted : May 24, 2017
Sponsor:
Collaborators:
Hamad Medical Corporation
Weill Cornell Medical College in Qatar
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
Identify a biologic (molecular) basis for the increased susceptibility of cigarette smokers to pulmonary TB (Mtb) by testing the hypothesis that smoking reprograms AM polarization towards a distinct phenotype associated with impaired host defense function against Mtb and that normalization of that phenotype via therapeutic modulation of the Alveolar Macrophage (AM) polarization or smoking cessation can restore the anti-Mtb host defense function of AM.

Condition or disease
Tuberculosis Chronic Obstructive Pulmonary Disease

Detailed Description:
Samples from Non-Smokers with TB, Smokers with TB and Smokers with COPD and TB will be collected in Qatar under JIRB 14-00055. All subjects will be undergoing a clinical bronchoscopy as part of their disease evaluation and will be asked to give additional samples for research. All "in vivo" processing of specimens from subjects with TB will be performed in Qatar. Mycobacterium tuberculosis infection (Mtb) continues to have a detrimental impact of public health worldwide. Based on the epidemiological evidence linking smoking, COPD and Mtb, and our preliminary data we hypothesize that smoking reprograms Alveolar Macrophages (AM) polarization towards a distinct phenotype associated with impaired host defense function against Myobacterium tuberculosis (Mtb) and that normalization of that phenotype via therapeutic modulation of the Alveolar Macrophages (AM) polarization or smoking cessation can restore the anti-Mtb host defense function of AM.

Study Type : Observational
Actual Enrollment : 0 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biologic Basis Of Increased Susceptibility Of Smokers To Pulmonary Infection With Mycobacterium Tuberculosis
Study Start Date : January 2014
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Group/Cohort
Individuals with TB

Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following:

  1. Symptoms consistent with TB
  2. Chest X-rays and or chest CT consistent with TB
  3. Positive PPD test
  4. Positive sputum test
Smokers

Active smoker as evidenced by self report and urine nicotine >30 ng/mL and urine cotinine >50 ng/mL

Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following:

  1. Symptoms consistent with TB
  2. Chest X-rays and or chest CT consistent with TB
  3. Positive PPD test
  4. Positive sputum test
Non-smokers

Never smokers is defined as someone who has smoked < 100 cigarettes per lifetime and whose urine nicotine <2 ng/mL and urine cotinine <5 ng/mL, at entry into the study

Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following:

  1. Symptoms consistent with TB
  2. Chest X-rays and or chest CT consistent with TB
  3. Positive PPD test
  4. Positive sputum test
Individuals with COPD

All study subjects should meet the "Lung Disease" protocol criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure

Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following:

  1. Symptoms consistent with TB
  2. Chest X-rays and or chest CT consistent with TB
  3. Positive PPD test
  4. Positive sputum test



Primary Outcome Measures :
  1. Alveolar Macrophage [ Time Frame: 1 week ]
    Changes in alveolar macrophage


Biospecimen Retention:   Samples With DNA
Blood Biological material from the lungs


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Recruitment will be from the referral base of the responsible investigator and other physicians, and review of admissions and hospital database. Patients, who may qualify for this study, will be identified by chart review, physician referral, and recruited by study investigators. The source of potential subjects will be the population of potential subjects with TB (smokers or non smokers), and with both TB and COPD, as defined before. Accrual will be random with no bias as to gender or racial/ethnic group.
Criteria

Smokers and Non-smokers with TB

Inclusion Criteria:

  • Must provide informed consent
  • Current smokers and non-smokers
  • Undergoing clinical bronchoscopy as required by their doctor for evaluation of their disease
  • Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed by at least one of the following:
  • Symptoms consistent with TB
  • Chest xray and or chest CT with TB
  • Positive PPD test
  • Positive sputum test

Exclusion Criteria:

  • Females who are pregnant or nursing
  • History of allergies to xylocaine, lidocaine, versed, valium, atropine, isoproterenol, terbutaline, aminophylline, or any local anesthetic

Smokers with TB and COPD

Inclusion Criteria:

  • Must provide informed consent
  • Current smokers with COPD
  • Undergoing clinical bronchoscopy as required by their doctor for evaluation of their disease
  • Diagnosis of pulmonary tuberculosis without extra-pulmonary TB, confirmed bu at least one of the following:
  • Symptoms consistent with TB
  • Chest xray and or chest CT consistent with TB
  • Positive PPD test
  • Positive sputum test

Exclusion Criteria:

  • Non-smokers
  • Females who are pregnant or nursing
  • History of allergies to xylocaine, lidocaine, versed, valium, atropine, isoproterenol, terbutaline, aminophylline, or any local anesthetic

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02021747


Locations
Qatar
Hamad Medical Corporation
Doha, Qatar
Sponsors and Collaborators
Weill Medical College of Cornell University
Hamad Medical Corporation
Weill Cornell Medical College in Qatar
Investigators
Principal Investigator: Ronald Crystal, MD Weill Medical College of Cornell University

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT02021747     History of Changes
Other Study ID Numbers: 14-00055 [JIRB]
NPRP 5-400-3-107 ( Other Identifier: Qatar National Research Fund )
11262/11 ( Other Identifier: HMC IRB )
First Posted: December 27, 2013    Key Record Dates
Last Update Posted: May 24, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All results of the proposed studies will be published in international peer-reviewed scientific journals, presented at meetings in Qatar, the regional and international conferences, and disseminated through the local Qatari media, seminars and lectures for high school and college students. The original data will be available to interested investigators using the conventional standards of biomedical science.

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Tuberculosis
Disease Susceptibility
Mycobacterium Infections
Respiratory Tract Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Disease Attributes
Pathologic Processes