Alpha-1 Antitrypsin DeficiencyNCT02810327
Alpha-1 Carrier Genomics Study
An observational study of Alpha-1 Antitrypsin Deficiency and Emphysema, run by Medical University of South Carolina at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency, Emphysema, COPD
- What is being tested?
- Genetic Sequencing
- How many people
- 117 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Apr 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Signed informed consent
- PiMZ individuals who fall into the lower quartile of AAT levels.
Who cannot join
- Age <18 years
- Known homozygous or compound heterozygous classic severe AATD (e.g. PiSZ, ZZ, Znull)
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina. Division of Pulmonary and Critical Care Medicine
Charleston, South Carolina, 29425
About this study
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.
Read the 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.
- Conditions
- Alpha-1 Antitrypsin Deficiency, Emphysema, COPD, Smoking
- Being tested
- Genetic Sequencing
- Keywords
- Alpha-1 antitrypsin deficiency, AATD, Alpha-1, SERPINA1, MZ, Carrier, Heterozygote, Smoking, COPD, Emphysema, Sequencing
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Emphysema, Pulmonary Disease, Chronic Obstructive, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic SequencingGenetic
Sequencing of the SERPINA1 gene
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Genetic: Genetic Sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Abnormal Sequences in SERPINA1 Genes
Additional SERPINA1 variant of known or possible significance detected by next generation sequencing.
Measured: End of study NGS Result
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2016 (estimated)
- Study startFeb 2015
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- CSL Behring
- Responsible party
- Sponsor
- Investigators
- Charlie Strange, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02810327
- Sponsor's protocol ID
- Pro00036911
- Status last verified
- May 2019
- First submitted
- 20 Jun 2016
- Last updated
- 22 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 17389752Molloy 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.
PubMed 24428606Eisner 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.
PubMed 15947299Foil 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.
PubMed 30254761
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alpha-1 Carrier Genomics Study
- ClinicalTrials.gov ID
- NCT02810327
- Acronym / sponsor ID
- Pro00036911
- Conditions
- Alpha-1 Antitrypsin Deficiency, Emphysema, COPD, Smoking
- Keywords
- Alpha-1 antitrypsin deficiency, AATD, Alpha-1, SERPINA1, MZ, Carrier, Heterozygote, Smoking
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- CSL Behring
- Study start
- Feb 2015 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 22 Jun 2016 (estimated)
- Results
- Posted 22 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MZ heterozygote with symptoms of COPD | – | Genetic: Genetic SequencingIndividuals 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 | – | Genetic: Genetic SequencingIndividuals 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Signed informed consent
- PiMZ individuals who fall into the lower quartile of AAT levels.
Key exclusion criteria (2 listed)
- Age <18 years
- Known homozygous or compound heterozygous classic severe AATD (e.g. PiSZ, ZZ, Znull)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genetic SequencingSequencing of the SERPINA1 gene | Genetic | MZ heterozygote with symptoms of COPD, MZ heterozygote without symptoms of COPD |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17389752Demeo 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.
- Background: PubMed 24428606Molloy 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.
- Background: PubMed 15947299Eisner 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.
- Derived from this study: PubMed 30254761Foil 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.
Related trials for Alpha-1 Antitrypsin Deficiency
RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 3
A Non-inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Doses of Weekly SC Alpha1-PI 15% Compared With Corresponding Standard IV Alpha1-PI in Participants With Alpha1-Antitrypsin Deficiency (AATD)
Alpha 1 Antitrypsin Deficiency
RecruitingPhase 1
A Study of AIR-001 in Adults With Alpha-1 Antitrypsin Deficiency (AATD)
Alpha 1 Antitrypsin Deficiency
Not yet recruitingPhase 1/2
A Study of the Safety and Efficacy of Prime Editing (PM647a) in Participants With Alpha-1 Antitrypsin Deficiency
Alpha-1 Antitrypsin Deficiency, Alpha-1 Antitrypsin Deficiency-associated Lung Disease
RecruitingPhase 1/2
A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants With Pi*ZZ AATD
Alpha-1 Antitrypsin Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charlie Strange, MD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alpha-1 Antitrypsin Deficiency and Emphysema, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Abnormal Sequences in SERPINA1 Genes (time frame: End of study NGS Result). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02810327, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019; AzTrials last refreshed its copy on 27 Oct 2026.