Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease (A1BC)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alpha 1-Antitrypsin Deficiency; Genetic Disease

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. 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.

• Study Type: Observational
• Enrollment (Actual): 286

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • University of California - Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Alpha-1 Antitrypsin Deficiency genotype ZZ across the United States.

Description

Inclusion Criteria:

1. Males and females aged 18 years and older
2. Patients with known Alpha-1 Anti-trypsin deficiency (PiZZ)
3. Be an existing member of the Alpha-1 Foundation Clinical Cohort (Alpha-1 Foundation Research Registry)
4. Willingness to perform study procedures of Chest CT, blood biomarker determination, questionnaire completion, and lung function testing.

Exclusion Criteria:

1. AATD non-PiZZ status, including carriers
2. Pregnancy at the time of the screening visit
3. COPD exacerbation or other pulmonary infection within 6 weeks of baseline visit
4. Previous lung or liver transplantation or currently on the transplant list

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Moderate to Advanced Emphysema; Patients with moderate or advanced Emphysema as measured by baseline inspiratory PERC-15 below the study median
Minimal Emphysema; Patients with minimal emphysema as measured by baseline inspiratory PERC-15 above the study median

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Alpha-1 Foundation
• Investigators: Study Chair: Charlie Strange, MD, Medical University of South Carolina; Principal Investigator: Jeanine M D'Armiento, MD, PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: March 17, 2022
• First Submitted That Met QC Criteria: March 17, 2022
• First Posted (Actual): March 28, 2022

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Alpha-1; PiZZ
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: AAAS8713; 1UG3HL152323 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study is part of a larger research study where one of the objectives is to create a AATD de-identified, public use repository of data. This repository will be query based, and any sub-projects that stem from this will need to abide by the appropriate Human Subjects Protection, GCP guidelines (i.e., IRB protocol, local IRB approval, DUA, Release of Information) and be reviewed by the research committee including the Alpha-1 Foundation prior to release of any de-identified data.
• IPD Sharing Time Frame: After first 3 years of data collection and preliminary analysis
• IPD Sharing Access Criteria: De-identified data will be available via i2b2 with proper protocol and IRB regulatory documentation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No