PiMZ Longitudinal Cohort (PiMZ Logic)

NCT06505603 | Recruiting DMC

• 1 other identifier: AAAU9605
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Alpha 1-Antitrypsin Deficiency; Emphysema or COPD

Keywords

Alpha-1; Biomarker; PiMZ

Outcome Measures

Primary Outcomes (2)

• Change in lung density over three years

  Change in lung density over three years determined by using the 15th percentile point (PERC-15) of Hounsfield units in inspiratory high resolution CT scans.

  3 years

• Decline of PERC-15 (15th percentile) over three years

  Rate of decline of PERC-15 over three years. PERC-15 provides the Hounsfield unit point below which 15% of all voxels are distributed. The lowest threshold is -1,000 HU. The lower the PERC-15 values are, the more CT-quantified emphysema is present.

  3 years

Study Arms (1)

Emphysema

FEV1/FVC \<70%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• Males and females aged 18 years and older
• Understand the study procedures, risks, benefits, purpose
• Able and willing to comply with the study procedures
• Have PiMZ alpha-1 antitrypsin deficiency
• Post bronchodilator FEV1 \< 80% predicted AND post bronchodilator FEV1/FVC \< 70%
• Be an existing member of the Alpha-1 Foundation Clinical Cohort (also known as the Alpha-1 Foundation Research Registry)
• Agree to have the data collected in this study be shared with the Alpha-1 Foundation Research Registry

You may not qualify if:

• AATD non-PiMZ status, including carriers
• Current lung, hematologic, or solid organ malignancy other than skin or cervical Stage 1 cancers within the past 3 years
• COPD exacerbation or other pulmonary infection within 6 weeks of baseline visit
• Pregnancy at the time of the screening visit
• Inability to lie still in a supine position for 15 minutes during CT acquisition
• Inability to perform quality-controlled lung function testing
• Allergy to albuterol
• Currently receiving intravenous or subcutaneous immunoglobulin for any disease state
• Past or present major surgery on the lungs including pneumonectomy or lobectomy. Wedge resections, past segmentectomy, and pleurodesis surgeries are allowed.
• Previous lung or liver transplantation or currently on the transplant list
• Decompensated cirrhosis
• Current presence of endobronchial coils or valves in the lung
• 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.
• 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.
• Patient with Automatic Implantable Cardioverter Defibrillator (AICD) and permanent pacemakers (PPM)

Sponsors & Collaborators

• Columbia University: lead
• Alpha-1 Foundation: collaborator

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

University of California- Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

National Jewish Health

Denver, Colorado, 80206, United States

NOT YET RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Genetic sequencing and analysis may be performed on the DNA or RNA in some samples (blood and nasal swab). The biological samples may be prepared and, in some cases, analyzed at the Irving Institute for Clinical and Translational Research, the UCLA Nasal Swab Biorepository, or the Institute of Genomic Medicine of Columbia University. The purpose of the genetic testing is to find out any genetic (inherited) trait that would make participants more likely to have lung injury. A clause in the consent form addresses future use of data and specimens and participants have a choice to accept or decline this use.

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Emphysema; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes

Study Officials

• Monica Goldklang, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabrina Palumbo, BS

CONTACT

2123053745; sp4461@cumc.columbia.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 17, 2024
• Study Start: May 30, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (5)