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Role of Genetic Factors in the Development of Lung Disease

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ClinicalTrials.gov Identifier: NCT00001532
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
Suburban Hospital
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:

This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease.

The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers.

Optional CT Sub-study

The standard CT scan will be compared to the low dose radiation CT scan for the 150 subjects enrolled in the sub-study to assess the variation between the two techniques. Specifically, the quantitative computer aided detection of lung CT abnormalities from LAM can be compared to assess whether low radiation dose CT exams is an alternative to conventional CT to monitor disease

status.

This optional sub-study will be offered to up to 100 adult subjects with lung disease and up to 50 children age 9 and older with CF. Children will not be enrolled in the optional CT sub-study unless they have had a standard CT scan for medical purposes to use in comparison. One additional low dose radiation CT scan of the chest may be done as part of this sub-study when these subjects have their next annual CT scan.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Pulmonary Fibrosis Tuberous Sclerosis Asthma Pulmonary Sarcoidosis Device: Toshibia Aquilion ONE CT Not Applicable

Detailed Description:
This study is designed to evaluate genetic mechanisms of lung disease by surveying polymorphic genes involved in respiratory function and examining gene expression in the lung cells of individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, history of infection, and genetic mutations consistent with lung pathology). Emphasis will be on defining the distribution of allelic variants of nitric oxide synthase, alpha 1-antitrypsin, and the cystic fibrosis transmembrane conductance regulator genes in patients and in age- and sex-matched healthy individuals in a control population.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3600 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Role of Genetic Factors in the Pathogenesis of Lung Disease
Actual Study Start Date : September 13, 1996
Estimated Primary Completion Date : August 1, 2025
Estimated Study Completion Date : August 1, 2025


Arm Intervention/treatment
No Intervention: Normal
comparison
Experimental: Pulmonary Disease
AAT deficiency, genetic lung diseases; CF, TSC, COPD,sarcoidosis, Wegener' s granulomatosis, diabetes mellitus, asthma, TSC, pulmonary fibrosis and mycobacterium infections.
Device: Toshibia Aquilion ONE CT
The Toshiba Aquilion ONE CT system is currently being used for studies in both general CT radiology and CT cardiac imaging. One of the unique aspects of the Aquilion ONE CT system is its ability to acquire whole organ volume images in a single rotation by utilizing an x-ray detector that is configured as 320 detector rows with a 0.5 mm width, providing a z-axis coverage of 16 cm of anatomy. In line with the evolutionary changes to CT systems, the Aquilion ONE will be upgraded with new technology that will expand its capabilities. The changes being made to the Aquilion ONE will provide enhancements to image acquisition capabilities, reduce ionizing radiation dose, and improve subject access to the system. All of these features assist in enhancing the safety of the currently installed Aquilion ONE CT system.




Primary Outcome Measures :
  1. Evaluate Pulmonary Diseases [ Time Frame: on going ]
    This is a preliminary study aimed at evaluating the role of hereditary factors in the pathogenesis of AAT deficiency, genetic lung diseases; CF, TSC, COPD, sarcoidosis, Wegener's granulomatosis, diabetes mellitus, asthma, TSC, pulmonary fibrosis and mycobacterium infections. The study includes a case-control comparison of the distribution of genetic variants of nitric oxide synthases and other candidate genes involved in pulmonary function. Analysis of data and/or samples from imaging studies, pulmonary function tests, and other clinical evaluations; blood, urine, saliva, and cheek swab samples; circulating LAM cells; dermatological evaluation and skin biopsies



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Inclusion criteria for patients with AAT deficiency include: (1) Diagnosis of AAT with a confirmed phenotype considered in the high risk category; (2) Clinical phenotype consistent with potential genetic diseases and other genetic causes of lung diseases (3) symptoms consistent with pulmonary disease; (4) chest x-ray consistent with pulmonary disease; (5) pulmonary function tests consistent with pulmonary disease; (6) smokers, defined as individuals who are current smokers (1 pack per day for at least 2 years) and nonsmokers, defined as never-smokers or ex-smokers who have quit smoking three or more years ago;

Inclusion criteria for individuals with chronic obstructive pulmonary diseases include:

  1. symptoms consistent with pulmonary disease
  2. chest x-ray consistent with pulmonary disease
  3. pulmonary function tests consistent with pulmonary disease;
  4. smokers, defined as individuals who are current smokers (1 pack per day for at least 2 years) and nonsmokers, defined as never-smokers or ex-smokers who have not smoked for three or more years.

Inclusion criteria for patients with cystic fibrosis include a defined genetic mutation (i.e., any of the known variants of the CFTR gene, such as delta F508 allele) or a cystic fibrosis phenotype and clinical features consistent with this disease. Children with cystic fibrosis over eight years of age may be included.

Patients with established diagnoses of sarcoidosis; mycobacterial infections; TSC (definite or possible); cystic lung diseases including genetic diseases; lymphangioleiomyomatosis or diseases associated with lymphatic disorders; history of pneumothorax; pulmonary fibrosis; asthma; histiocytosis X and diabetes mellitus will be included in this protocol. Relatives of patients may also be seen under this protocol. Children with lymphangiomatosis who are two years of age or older may be included. Participants with asthma may be enrolled at Suburban Hospital.

Research volunteers in the pulmonary control group are defined as individuals with no pulmonary disease (e.g. rheumatoid arthritis without evidence of pulmonary disease). Research volunteers in the diabetes control group are defined as individuals with no history of diabetes, coronary artery disease, or pulmonary disease.

Pregnant and or nursing women can be included in accordance with Federal Regulations at Subpart B of 45 CFR 46. Subjects who are pregnant and or nursing will be excluded from procedures during their pregnancy that are greater than minimal risk, until they are no longer pregnant and/or nursing. Procedures that will not be completed while the subject is pregnant and/or nursing including: PFTs, Six Minute Walk Test, thoracentesis, bronchoscopy, and measurements with imaging modalities requiring contrast or with radiation exposure such as Chest x-ray, CT scan, MRI. Allowing subjects to be included in the study may glean important information about individuals with uncommon pulmonary disease during and post pregnancy.

Patients with abnormalities in ADP-ribosyltransferases, ADP-ribosyl-acceptor hydrolases, and their substrates. Children who are two years of age or older may be studied if they have a known defect in ADP-ribosylation, or if they have a family member with a defect in ADP-ribosylation and may be affected.

EXCLUSION CRITERIA:

Exclusion criteria for all participants include:

  1. age less than 18 or greater than 90 except for NIH patients with diseases /disorders as described in this protocol (except cystic fibrosis, lymphangiomatosis or defects in ADP-ribosylation) who are 16 years of age or older, patients with cystic fibrosis who are over eight years of age, patients who are two years of age or older with lymphangiomatosis or a known defect in ADP-ribosylation, or who have a family member with a defect in ADP-ribosylation, or unless patient-specific IRB approval is obtained and;
  2. inability to obtain reliable pulmonary function testing. As clarification, healthy volunteers, relatives of patients (except as noted for an ADP-ribosylation defect), and asthmatic patients from Suburban Hospital will be excluded if less than 18 or greater than 90 years of age.

Exclusion criteria for participating in the bronchoscopy portion of the study are:

  1. presence of any contraindication for fiberoptic bronchoscopy, with lavage and/or bronchial brushing;
  2. advanced stage of a pulmonary or a systemic illness such that the risk is judged to be significant even in the absence of a specific contraindication to the procedure
  3. allergy to topical anesthetic (e.g., lidocaine)
  4. current or recent respiratory infection (within the last 4 weeks)
  5. pregnancy or lactation
  6. age less than 18 or greater than 65.

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): NCT00001532


Contacts
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Contact: Tania R Machado (301) 496-3632 tania.machado@nih.gov
Contact: Joel Moss, M.D. (301) 496-1597 mossj@nhlbi.nih.gov

Locations
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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 Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Suburban Hospital
Investigators
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Principal Investigator: Joel Moss, M.D. National Heart, Lung, and Blood Institute (NHLBI)

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00001532     History of Changes
Other Study ID Numbers: 960100
96-H-0100
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: September 27, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Genetic Polymorphism
Nitric Oxide Synthesis
Alpha 1-Antitrypsin
Candidate Genes
Lung Pathology
Lung Disease
Cystic Fibrosis
Asthma
Additional relevant MeSH terms:
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Tuberous Sclerosis
Cystic Fibrosis
Lung Diseases
Pulmonary Fibrosis
Sarcoidosis, Pulmonary
Sarcoidosis
Fibrosis
Respiratory Tract Diseases
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Lung Diseases, Interstitial