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NCT06505603Recruiting

PiMZ Longitudinal Cohort (PiMZ Logic)

Columbia University

Start Date

5/30/2025

Completion Date

2/1/2029

Summary

Alpha-1 Anti-trypsin Deficiency (AATD) is a genetic disease with lung and liver disease presentations. Presentations are variable in the heterozygous population, the most predominant genotype being PiMZ. The purpose of this study in PiMZ heterozygous patients is to examine the density of the lung as measured by chest computed tomography (CT) and determine if existing emphysema predicts changes in the rate of subsequent emphysema or changes in CT, serum or plasma biomarkers of interest. The overarching goal is to develop biomarkers pertinent to the PiMZ patient that can be used in interventional trials since lung function changes do not typically inform disease progression in AATD.

Detailed Description

Progression of lung disease in patients with Alpha-1 Anti-trypsin deficiency is variable and while some patients may have stable lung function over many years, some progress and deteriorate rapidly. Currently there are no predictors that would help identify patient at risk of rapid deterioration in the PiMZ patient population. The aim of this study is to identify markers and features in CT imaging that may allow identification of these patients early before deterioration. To achieve this, the study will follow a cohort of patients with confirmed Alpha-1 Anti-trypsin deficiency (MZ genotype) and obstructive lung disease and measure a number of biomarkers in blood and sputum and obtain high resolution CT scans at baseline and again three years later. If the study is able to determine markers that allow the identification of patients at risk early, the investigator may be able to study early interventions in later studies and possibly find ways to avoid serious complications. Patients will be followed longitudinally to assess deterioration of lung function. Study procedures include: Review of medical history and medication history, blood draw, spriometry, induced sputum (at some sites), completion of questionnaires and CT Chest scan. All of the mentioned procedures above will be performed on enrollment and repeated at 18 months and 36 months, with the exception of monthly Alpha- net exacerbation questionnaires.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Males and females aged 18 years and older 2. Understand the study procedures, risks, benefits, purpose 3. Able and willing to comply with the study procedures 4. Have PiMZ alpha-1 antitrypsin deficiency 5. Post bronchodilator FEV1 \< 80% predicted AND post bronchodilator FEV1/FVC \< 70% 6. Be an existing member of the Alpha-1 Foundation Clinical Cohort (also known as the Alpha-1 Foundation Research Registry) 7. Agree to have the data collected in this study be shared with the Alpha-1 Foundation Research Registry Exclusion Criteria: 1. AATD non-PiMZ status, including carriers 2. Current lung, hematologic, or solid organ malignancy other than skin or cervical Stage 1 cancers within the past 3 years 3. COPD exacerbation or other pulmonary infection within 6 weeks of baseline visit 4. Pregnancy at the time of the screening visit 5. Inability to lie still in a supine position for 15 minutes during CT acquisition 6. Inability to perform quality-controlled lung function testing 7. Allergy to albuterol 8. Currently receiving intravenous or subcutaneous immunoglobulin for any disease state 9. Past or present major surgery on the lungs including pneumonectomy or lobectomy. Wedge resections, past segmentectomy, and pleurodesis surgeries are allowed. 10. Previous lung or liver transplantation or currently on the transplant list 11. Decompensated cirrhosis 12. Current presence of endobronchial coils or valves in the lung 13. Clinically significant bronchiectasis as defined by the investigator. In general, this would exclude patients with chronic infection of the lungs requiring treatment within the past 6 months including non-tuberculous mycobacterial disease, chronic fungal disease, allergic bronchopulmonary aspergillosis, or known colonization of bronchiectasis with pseudomonas or stenotrophomonas species. 14. Participation in the active treatment arm of a therapeutic clinical trial at baseline visit unless using one of the Alpha-1 augmentation therapies in alternative doses. 15. Patient with Automatic Implantable Cardioverter Defibrillator (AICD) and permanent pacemakers (PPM) 16. Patient receiving biologic immunomodulators that will affect the assessment of the serum biomarkers (as determined by the site PI) 17. Patient with pleural catheters 18. Any condition that in the opinion of the investigator might adversely influence the study outcome

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Conditions

Alpha 1-Antitrypsin DeficiencyEmphysema or COPD

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35233

United States

University of California- Los Angeles

Los Angeles, California 90095

United States

National Jewish Health

Denver, Colorado 80206

United States

University of Chicago

Chicago, Illinois 60637

United States

Columbia University Irving Medical Center

New York, New York 10032

United States