Alpha-1 Carrier Genomics Study

NCT02810327 | Completed Results

• 1 other identifier: Pro00036911
• Study Type: observational
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alpha-1 Antitrypsin Deficiency; Emphysema; COPD; Smoking

Keywords

Alpha-1 antitrypsin deficiency; AATD; Alpha-1; SERPINA1; MZ; Carrier; Heterozygote; Smoking; COPD; Emphysema; Sequencing

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Abnormal Sequences in SERPINA1 Genes

  Additional SERPINA1 variant of known or possible significance detected by next generation sequencing.

  End of study NGS Result

Study Arms (2)

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: Genetic Sequencing

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: Genetic Sequencing

Interventions

Genetic Sequencing GENETIC

Sequencing of the SERPINA1 gene

MZ heterozygote with symptoms of COPD; MZ heterozygote without symptoms of COPD

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

Individuals age 18 and over who have previously had testing for Alpha-1 antitrypsin deficiency with genotype MZ (PiMZ) results, and an alpha-1 antitrypsin level of less than 16.0uM (83mg/dL) are eligible to participate.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• CSL Behring: collaborator

Study Sites (1)

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

Charleston, South Carolina, 29425, United States

Location

Related Publications (4)

• 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.

  PMID: 17389752 BACKGROUND

• 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.

  PMID: 24428606 BACKGROUND

• 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.

  PMID: 15947299 BACKGROUND

• 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.

  PMID: 30254761 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Bloodspot collections for DNA and limited protein analysis

MeSH Terms

Conditions

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

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; Behavior

Results Point of Contact

• Title: Kimberly Brown Foil
• Organization: Medical University of South Carolina

foilk@musc.edu

843-792-6474

Study Officials

• Charlie Strange, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2016
• First Posted: June 22, 2016
• Study Start: February 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: July 22, 2019
• Results First Posted: July 22, 2019

Record last verified: 2019-05

Locations

US (1)