Alpha-1 Carrier Genomics Study

NCT ID: NCT02810327

Last Updated: 2019-07-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

117 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-02-28

Study Completion Date

2017-04-30

Brief Summary

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The goal of this study is to better understand why some Alpha-1 genotype MZ (PiMZ) individuals develop chronic obstructive pulmonary disease (COPD) while others do not. This study will examine portions of the Alpha-1 gene that are not routinely tested to determine whether other changes in this gene correlate with development and progression of COPD. Participation involves responding to questionnaires about lung health and history, and performing an at-home finger stick to obtain blood spots using a test kit that is mailed. The blood provided will be used for genetic testing and correlation of results with COPD history. Participants will receive their results and access to genetic counseling at the conclusion of the study.

Detailed Description

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Alpha-1 Antitrypsin Deficiency (AATD, Alpha-1) is the best established genetic risk factor for chronic obstructive pulmonary disease (COPD) and liver disease. Clinical presentation is heterogeneous in most genotypic populations of alpha-1 antitrypsin deficiency (AATD) and genetic variation in the Alpha-1 gene has been incompletely studied. Rare gene alterations that predispose to COPD risks of classic AATD in individuals without a classic homozygous deficiency genotype have not been studied and are important in understanding, testing and treating at-risk populations. Investigators hypothesize that SERPINA1 gene sequencing will find important sequence variations in previously assessed MZ individuals who have COPD compared to age, race, sex, AAT level and smoking status matched MZ individuals who do not have COPD.

The Alpha-1 Carrier Genomics study is a pilot study that will enroll up to 150 MZ individuals. COPD+ and COPD- individuals will be matched on age, sex, race and smoking history. Presence and severity of COPD is assessed by a COPD severity score on questionnaires. Participants will be mailed a test kit to obtain and return a blood sample by finger stick for the purpose of SERPINA1 gene sequencing. Gene sequencing will identify, if present, genomic signatures that may correlate with COPD in this cohort. Participants will receive their results and access to genetic counseling at the conclusion of this study.

Conditions

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Alpha-1 Antitrypsin Deficiency Emphysema COPD Smoking

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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MZ heterozygote with symptoms of COPD

Individuals who have previously had testing for Alpha-1 antitrypsin deficiency with genotype MZ (PiMZ) results. Individuals in this cohort have symptoms or clinical diagnosis of COPD.

Genetic Sequencing

Intervention Type GENETIC

Sequencing of the SERPINA1 gene

MZ heterozygote without symptoms of COPD

Individuals who have previously had testing for Alpha-1 antitrypsin deficiency with genotype MZ (PiMZ) results. Individuals in this cohort do not have symptoms or clinical diagnosis of COPD.

Genetic Sequencing

Intervention Type GENETIC

Sequencing of the SERPINA1 gene

Interventions

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Genetic Sequencing

Sequencing of the SERPINA1 gene

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent
2. PiMZ individuals who fall into the lower quartile of AAT levels.

Exclusion Criteria

1. Age \<18 years
2. Known homozygous or compound heterozygous classic severe AATD (e.g. PiSZ, ZZ, Znull)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CSL Behring

INDUSTRY

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charlie Strange, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

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Medical University of South Carolina. Division of Pulmonary and Critical Care Medicine

Charleston, South Carolina, United States

Site Status

Countries

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United States

References

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Demeo DL, Sandhaus RA, Barker AF, Brantly ML, Eden E, McElvaney NG, Rennard S, Burchard E, Stocks JM, Stoller JK, Strange C, Turino GM, Campbell EJ, Silverman EK. Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. Thorax. 2007 Sep;62(9):806-13. doi: 10.1136/thx.2006.075846. Epub 2007 Mar 27.

Reference Type BACKGROUND
PMID: 17389752 (View on PubMed)

Molloy K, Hersh CP, Morris VB, Carroll TP, O'Connor CA, Lasky-Su JA, Greene CM, O'Neill SJ, Silverman EK, McElvaney NG. Clarification of the risk of chronic obstructive pulmonary disease in alpha1-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med. 2014 Feb 15;189(4):419-27. doi: 10.1164/rccm.201311-1984OC.

Reference Type BACKGROUND
PMID: 24428606 (View on PubMed)

Eisner MD, Trupin L, Katz PP, Yelin EH, Earnest G, Balmes J, Blanc PD. Development and validation of a survey-based COPD severity score. Chest. 2005 Jun;127(6):1890-7. doi: 10.1378/chest.127.6.1890.

Reference Type BACKGROUND
PMID: 15947299 (View on PubMed)

Foil KE, Blanton MG, Sanders C, Kim J, Al Ashry HS, Kumbhare S, Strange C. Sequencing Alpha-1 MZ Individuals Shows Frequent Biallelic Mutations. Pulm Med. 2018 Sep 5;2018:2836389. doi: 10.1155/2018/2836389. eCollection 2018.

Reference Type DERIVED
PMID: 30254761 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Pro00036911

Identifier Type: -

Identifier Source: org_study_id

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