Clinical trial NCT05297812: Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease
Official title: Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease - Alpha-1 Biomarker Research Consortium (A1BC)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Alpha 1-Antitrypsin Deficiency
Genetic Disease
Keywords: Alpha-1
Biomarker
PiZZ
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Alpha-1 Foundation
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-03-28
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Alpha-1 Antitrypsin Deficiency genotype ZZ across the United States.

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.

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.

Eligibility 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, 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

Primary outcomes:
measure: Change in lung density over three years
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Columbia University
name: Jeanine M D'Armiento, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Charlie Strange, MD
role: STUDY_CHAIR
References: