Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease

Study Overview
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Brief Summary
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Alpha-1 Anti-trypsin Deficiency (AATD) is a genetic disease with lung and liver disease presentations. The purpose of this study 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 that can be used in interventional trials since lung function changes do not typically inform disease progression in AATD.

Detailed Description
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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. 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 and 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, complete Pulmonary Function Test (PFT), 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.

Official Title
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Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease - Alpha-1 Biomarker Research Consortium (A1BC)

Conditions
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Alpha 1-Antitrypsin Deficiency, Genetic Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18 years and older Patients with known Alpha-1 Anti-trypsin deficiency (PiZZ) Be an existing member of the Alpha-1 Foundation Clinical Cohort (Alpha-1 Foundation Research Registry) Willingness to perform study procedures of Chest CT, blood biomarker determination, sputum collection, questionnaire completion, and lung function testing. Exclusion Criteria: AATD non-PiZZ status, including carriers Pregnancy at the time of the screening visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Moderate to Advanced Emphysema<br>Patients with moderate or advanced Emphysema as measured by baseline inspiratory PERC-15 below the study median | |
| Minimal Emphysema<br>Patients with minimal emphysema as measured by baseline inspiratory PERC-15 above the study median | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lung density over three years | Change in lung density over three years determined by using the 15th percentile point of Hounsfield units in inspiratory high resolution CT scans (PERC-15) | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alpha-1, Biomarker, PiZZ