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

• ClinicalTrials.gov Identifier: NCT05297812
• Recruitment Status: Recruiting
• First Posted: March 28, 2022
• Last Update Posted: July 6, 2022
• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Alpha-1 Foundation
• Information provided by (Responsible Party): Jeanine D'Armiento, Columbia University

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 270 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Target Follow-Up Duration: 18 Months
• Official Title: Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease - Alpha-1 Biomarker Research Consortium (A1BC)
• Actual Study Start Date: March 23, 2022
• Estimated Primary Completion Date: February 2026
• Estimated Study Completion Date: February 2026

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Change in lung density over three years [ Time Frame: 3 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)

Biospecimen Retention:   Samples With DNA

Blood samples will be collected for analysis in the ongoing clinical trial as well as for banking to for a bio-repository for future AATD studies. Participants will have the option to agree/not agree to partake in the optional bio-repository.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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, sputum collection, questionnaire completion, and lung function testing.

Exclusion Criteria:

1. AATD non-PiZZ status, including carriers
2. Pregnancy at the time of the screening visit

Contacts and Locations

Contacts

Contact: Alexis Fisher; 212-305-3745; acf2163@cumc.columbia.edu

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35233

Contact: Dianne Freeman, BS, RRT 205-996-2709 dsmurphy@uabmc.edu

Contact: Necole Harris, MA, CRT 205-934-5555 nharris@uabmc.edu

Principal Investigator: James M Wells, MD, MSPH

Sub-Investigator: Surya P Bhatt, MD, MSPH

Sub-Investigator: Sandeep Bodduluri, PhD

United States, California

University of California - Los Angeles; Not yet recruiting

Los Angeles, California, United States, 90095

Contact: Brian Jung 310-794-2156 djung@mednet.ucla.edu

Contact: Roslynn McGill 310 825 2616 rmcgill@mednet.ucla.edu

Principal Investigator: Igor Barjaktarevic, MD, PhD

Sub-Investigator: Russell Buhr, MD, PhD

United States, Colorado

National Jewish Health; Not yet recruiting

Denver, Colorado, United States, 80206

Contact: Daniell Plomondon 303-270-2041 plomondond@njhealth.org

Principal Investigator: Robert A Sandhaus, MD, PhD

Sub-Investigator: Karina Serban, MD

United States, Florida

University of Florida; Not yet recruiting

Gainesville, Florida, United States, 32610

Contact: Vanessa Scheuble, CCRC 352-273-7589 vanessa.scheuble@medicine.ufl.edu

Principal Investigator: Mark L Brantly, MD

Sub-Investigator: Jorge Lascano, MD

United States, Illinois

University of Chicago; Not yet recruiting

Chicago, Illinois, United States, 60637

Contact: Spring A Maleckar, CCRC 773-834-4053 smaleckar@bsd.uchicago.edu

Principal Investigator: D. Kyle Hogarth, MD

United States, Massachusetts

Boston University; Not yet recruiting

Boston, Massachusetts, United States, 02118

Contact: Mark Dodge, MPH 617-358-2413 mdodge1@bu.edu

Principal Investigator: Andrew A Wilson, MD

United States, New York

Columbia University; Recruiting

New York, New York, United States, 10032

Contact: Alexis Fisher 212-305-3745 acf2163@cumc.columbia.edu

Principal Investigator: Jeanine M D'Armiento, MD, PhD

Sub-Investigator: Monica P Goldklang, MD

United States, North Carolina

University of North Carolina; Recruiting

Chapel Hill, North Carolina, United States, 27514

Contact: Caleb Hemphill, MS 984-974-2963 caleb_hemphill@med.unc.edu

Contact: Annette Babu 984-974-2963 annette_babu@med.unc.edu

Principal Investigator: Brad Drummond, MD, MHS

United States, South Carolina

Medical University of South Carolina; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Kristin Neff 843-792-1219 neffk@musc.edu

Contact: Susan Norton 843-792-6280 nortons@musc.edu

Principal Investigator: Charlie Strange, MD

Sub-Investigator: Margaret Hay, MD

United States, Utah

University of Utah; Recruiting

Salt Lake City, Utah, United States, 84108

Contact: Andriea Smith 801-587-7855 andriea.smith@hsc.utah.edu

Contact: Lisa Weaver 801-587-7855 Lisa.weaver@hsc.utah.edu

Principal Investigator: Cheryl Pirozzi, MD

Sub-Investigator: Barbara Cahill, MD

Sub-Investigator: Sean Callahan, MD

Sponsors and Collaborators

Columbia University

National Heart, Lung, and Blood Institute (NHLBI)

Alpha-1 Foundation

Investigators

• Principal Investigator: Jeanine M D'Armiento, MD, PhD; Columbia University
• Study Chair: Charlie Strange, MD; Medical University of South Carolina

More Information

• Responsible Party: Jeanine D'Armiento, Associate Professor of Medicine (in Anesthesiology), Columbia University
• ClinicalTrials.gov Identifier: NCT05297812
• Other Study ID Numbers: AAAS8713; 1UG3HL152323 ( U.S. NIH Grant/Contract )
• First Posted: March 28, 2022
• Last Update Posted: July 6, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Time Frame: After first 3 years of data collection and preliminary analysis
• Access Criteria: De-identified data will be available via i2b2 with proper protocol and IRB regulatory documentation

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jeanine D'Armiento, Columbia University:

Alpha-1; Biomarker; PiZZ

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency; Genetic Diseases, Inborn; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Subcutaneous Emphysema; Emphysema; Pathologic Processes