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| Name | Class |
|---|---|
| CSL Behring | INDUSTRY |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genetic Sequencing | Genetic | Sequencing of the SERPINA1 gene |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Charlie Strange, MD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina. Division of Pulmonary and Critical Care Medicine | Charleston | South Carolina | 29425 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17389752 | Background | 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. | |
| 24428606 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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: Sequencing of the SERPINA1 gene |
| FG001 | 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: Sequencing of the SERPINA1 gene |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Individuals age 18 and over with previous MZ results for Alpha-1 antitrypsin deficiency and AAT level in the lower MZ quartile (<16uM).
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| ID | Title | Description |
|---|---|---|
| BG000 | 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: Sequencing of the SERPINA1 gene |
| BG001 | MZ Heterozygote Without Symptoms of COPD |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 14 consented participants did not return their test kits and/or questionnaires. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Abnormal Sequences in SERPINA1 Genes | Additional SERPINA1 variant of known or possible significance detected by next generation sequencing. | Posted | Number | participants | End of study NGS Result | samples | samples |
|
1 year, 1 month
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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: Sequencing of the SERPINA1 gene |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kimberly Brown Foil | Medical University of South Carolina | 843-792-6474 | foilk@musc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 1, 2016 | Jan 24, 2019 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 12, 2016 | Jan 24, 2019 | ICF_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 1, 2016 | Jan 24, 2019 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D019896 | alpha 1-Antitrypsin Deficiency |
| D004646 | Emphysema |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D012907 | Smoking |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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Bloodspot collections for DNA and limited protein analysis
| 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. |
| 15947299 | 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. |
| 30254761 | Derived | 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. |
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: Sequencing of the SERPINA1 gene |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Full Range |
| years |
|
| Sex: Female, Male | 14 consented participants did not return their test kits and/or questionnaires. | Count of Participants | Participants |
|
| Race (NIH/OMB) | 14 consented participants did not return their test kits and/or questionnaires. | Count of Participants | Participants |
|
|
|
|
| 0 |
| 76 |
| 0 |
| 76 |
| 0 |
| 76 |
| EG001 | 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: Sequencing of the SERPINA1 gene | 0 | 41 | 0 | 41 | 0 | 41 |
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013352 | Subcutaneous Emphysema |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008173 | Lung Diseases, Obstructive |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D001519 | Behavior |
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|