Alpha-1 Carrier Genomics Study

COPD Clinical Trial

Official title:

Alpha-1 Carrier Genomics Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02810327
• Other study ID #: Pro00036911
• Status: Completed
• Start date: February 2015
• Est. completion date: April 2017

Study information

• Verified date: May 2019
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha-1 Antitrypsin Deficiency
• COPD
• Emphysema
• Pulmonary Emphysema
• Smoking

Intervention

Genetic:
• Genetic Sequencing
Sequencing of the SERPINA1 gene

Locations

Country	Name	City	State
United States	Medical University of South Carolina. Division of Pulmonary and Critical Care Medicine	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	CSL Behring

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Epub 2007 Mar 27. — View Citation

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. — View Citation

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 a1-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med. 2014 Feb 15;189(4):419-27. doi: 10.1164/rccm.201311-1984OC. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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