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Alpha-1 Carrier Genomics Study

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ClinicalTrials.gov Identifier: NCT02810327
Recruitment Status : Completed
First Posted : June 22, 2016
Results First Posted : July 22, 2019
Last Update Posted : July 22, 2019
Sponsor:
Collaborator:
CSL Behring
Information provided by (Responsible Party):
Medical University of South Carolina

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.

Condition or disease Intervention/treatment
Alpha-1 Antitrypsin Deficiency Emphysema COPD Smoking Genetic: Genetic Sequencing

Detailed 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.

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Study Type : Observational
Actual Enrollment : 117 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Alpha-1 Carrier Genomics Study
Actual Study Start Date : February 2015
Actual Primary Completion Date : April 2017
Actual Study Completion Date : April 2017


Group/Cohort Intervention/treatment
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
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: Genetic Sequencing
Sequencing of the SERPINA1 gene




Primary Outcome Measures :
  1. Number of Participants With Abnormal Sequences in SERPINA1 Genes [ Time Frame: End of study NGS Result ]
    Additional SERPINA1 variant of known or possible significance detected by next generation sequencing.


Biospecimen Retention:   Samples With DNA
Bloodspot collections for DNA and limited protein analysis


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810327


Locations
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United States, South Carolina
Medical University of South Carolina. Division of Pulmonary and Critical Care Medicine
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
CSL Behring
Investigators
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Principal Investigator: Charlie Strange, MD Medical University of South Carolina
  Study Documents (Full-Text)

Documents provided by Medical University of South Carolina:
Study Protocol  [PDF] April 1, 2016
Informed Consent Form  [PDF] May 12, 2016
Statistical Analysis Plan  [PDF] April 1, 2016

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT02810327    
Other Study ID Numbers: Pro00036911
First Posted: June 22, 2016    Key Record Dates
Results First Posted: July 22, 2019
Last Update Posted: July 22, 2019
Last Verified: May 2019
Keywords provided by Medical University of South Carolina:
Alpha-1 antitrypsin deficiency
AATD
Alpha-1
SERPINA1
MZ
Carrier
Heterozygote
Smoking
COPD
Emphysema
Sequencing
Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency
Pulmonary Emphysema
Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Liver Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema