Genomic Research in Alpha-1 Antitrypsin Deficiency

Completed

Conditions studied: Alpha 1 Antitrypsin Deficiency, AATD

In brief

This project is designed to examine the interaction between the microflora in the lower airway and the concentration of a serum protein called alpha-1 antitrypsin. The hypothesis is that alpha-1 antitrypsin impacts the diversity and content of the lower airway microflora, resulting in a less inflammatory airway. The Specific Aims are: 1. To compare the lower respiratory tract microbiome and virome population diversity and content in age and GOLD stage matched PiZZ individuals not receiving augmentation therapy, PiZZ individuals on augmentation therapy, PiMZ individuals not receiving augmentation therapy, and PiMM individuals with chronic obstructive pulmonary disease (COPD). 2. Determine correlations between bronchoalveolar lavage (BAL) and peripheral blood gene expression patterns and patterns in lung microbial and viral populations across all cohorts. 3. Correlate the presence or absence of computed tomography (CT) bronchiectasis and bronchiolectasis with patterns in the microbiome population diversity and content. 4. To identify and define novel molecular phenotypes of Alpha-1 Antitrypsin Deficiency (AATD) based on computational integration of clinical, transcriptomic, and microbiome data.

Key facts

Study ID

NCT01832220

Run by

University of Pittsburgh

People needed

140

Starts

2013-05-01

Expected to finish

2015-09-01

Last updated by the study team

2016-01-12

Who can join

Age: 40 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age between age 40 and 80 (inclusive) at Baseline Visit
• Alpha-1 Antitrypsin genotype PiZZ or PiMZ
• Able to tolerate and willing to undergo study procedures
• Signed informed consent

You may not qualify if…

• History of comorbid condition severe enough to significantly increase risks based on investigator discretion
• Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia
• Partial pressure of oxygen in the blood (PaO2) on room air at rest <50 mmHg or saturation level of oxygen in hemoglobin(SaO2) on room air at rest <85%
• Post bronchodilator Forced Expiratory Volume in One Second (FEV1)<30% predicted
• Use of anticoagulation (patients on warfarin or clopidogrel will be excluded; patients on aspirin alone can be studied even with concurrent use)
• Dementia or other cognitive dysfunction which in the opinion of the investigator would prevent the participant from consenting to the study or completing study procedures
• Active pulmonary infection with tuberculosis
• History of pulmonary embolism in the past 2 years
• Non-COPD obstructive disease (various bronchiolitides, sarcoid, LAM, histiocytosis X) or parenchymal lung disease, pulmonary vascular disease, pleural disease, severe kyphoscoliosis, neuromuscular weakness, or other cardiovascular and pulmonary disease, that, in the opinion of the investigator, limit the interpretability of the pulmonary function measures
• Prior significant difficulties with pulmonary function testing
• Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers
• Hypersensitivity to or intolerance of all drugs required for sedation during conscious sedation bronchoscopy.
• History of Lung volume reduction surgery, lung resection or bronchoscopic lung volume reduction in any form
• History of lung or other organ transplant
• History of large thoracic metal implants (e.g., Automatic Implantable Cardioverter Defibrillators (AICD) and/or pacemaker) that in the opinion of the investigator limit the interpretability of CT scans
• Currently taking >=10mg a day/20mg every other day of prednisone or equivalent systemic corticosteroid
• Currently taking any immunosuppressive agent excepting systemic corticosteroids
• History of lung cancer or any cancer that spread to multiple locations in the body
• Current illicit substance abuse, excluding marijuana
• Known HIV/AIDS infection
• History of or current exposure to chemotherapy or radiation treatments that, in the opinion of the investigator, limits the interpretability of the pulmonary function measures.
• Has a BMI > 40 kg/m2 at baseline exam
• Current or planned pregnancy within the study course.
• Currently institutionalized (e.g., prisons, long-term care facilities)
• Have a genotype of PiMZ and ever received intravenous or inhaled alpha-1 augmentation therapy (Alpha-1 Proteinase Inhibitor, A1PI)

Where it is running

• Arizona Health Sciences Center — Tucson, Arizona, United States
• University of California - San Francisco — San Francisco, California, United States
• National Jewish Health — Denver, Colorado, United States
• Yale University — New Haven, Connecticut, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• University of Pennsylvania — Philadelphia, Pennsylvania, United States
• University of Pittsburgh — Pittsburgh, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• Vanderbilt University — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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