Alpha-1 Antitrypsin Deficiency Adult Liver Study
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ClinicalTrials.gov Identifier: NCT02014415 |
Recruitment Status :
Recruiting
First Posted : December 18, 2013
Last Update Posted : February 15, 2022
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Condition or disease | Intervention/treatment |
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Alpha-1 Antitrypsin Deficiency | Procedure: Liver Biopsy (Biopsy Group Only) |
Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder resulting in a low level of a protein called alpha-1 antitrypsin (AAT). This deficiency can cause life-threatening liver disease and/or lung disease at various ages. Some patients experience life-threatening liver disease in childhood or liver cancer as adults. There is no specific treatment for AAT related liver disease. Some patients develop emphysema as young adults, while some patients remain healthy throughout their lives. Differences in the environment or in other genes may explain such inconsistency in the disease.
The primary objective of this multi-center study is to assess the natural history of individuals with Pi-ZZ AAT deficiency, identify biomarkers for the progression of liver disease and construct a database capable of linking cohort data with repository biospecimens. The secondary objective is to analyze components of the demographic, social, and family history associated with more severe liver disease.
This study will examine the natural history of liver disease by recording participant's family history, medical history, current health, laboratory test results, and medical treatment(s). Participants may complete brief research questionnaires about their physical and mental health, diet, alcohol intake, and smoke, environmental and occupational (work) exposures.
At least 120 Pi-ZZ AAT deficient adults with no previous history of liver disease, moderate-severe liver disease, or post liver transplant, will be enrolled at one of three sites. Eligible subjects will participate in one of the following study arms:
- Liver Biopsy
- Known Severe Liver Disease - subjects not meeting Biopsy Group eligibility due to the presence of advanced liver disease
- Post Liver Transplant - subjects who have previously undergone a liver transplant
At the time of enrollment, each participant will be assigned a unique study identification (ID) number. All participant information recorded and samples collected for the study will be saved by this unique number. All blood, tissue and genetic samples collected will be sent to a secured repository for future retrieval and study. The process of coding data and samples lessens the chances of a breach in confidentiality.
The length of study participation, tests and activities performed specifically for research will be determined by the enrollment group. Subjects in the Biopsy and Known Severe Liver Disease groups participate in the study for 5 years (enrollment and four annual follow-up visits). Both groups undergo a physical exam, diagnostic abdominal ultrasound, pulmonary function testing and the collection of serum, plasma and blood for routine laboratory and genetic testing (Induced Pluripotent Stem Cells (iPS cells), microRNA and DNA). However, only the Biopsy Group participants undergo a liver biopsy and FibroScan at enrollment, and again in Year 5. The liver tissue samples will help the researchers learn what causes liver disease in some patients and how the liver disease progresses.
Subjects in the Post Liver Transplant group have a single study visit to record their history, complete questionnaires and perform pulmonary function testing. In addition, whole blood for DNA analysis will be collected from these participants.
Based on their study arm assignment, participants will receive copies of their diagnostic abdominal ultrasound, pulmonary function test, routine laboratory test and liver biopsy pathology results, to share with their primary care physician.
Study Type : | Observational [Patient Registry] |
Estimated Enrollment : | 120 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Target Follow-Up Duration: | 5 Years |
Official Title: | Alpha-1 Antitrypsin Deficiency Adult Clinical and Genetic Linkage Study |
Study Start Date : | December 2013 |
Estimated Primary Completion Date : | September 2023 |
Estimated Study Completion Date : | September 2023 |

Group/Cohort | Intervention/treatment |
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Liver Biopsy
Participants will provide liver tissue specimens collected at the time of liver biopsy, to determine the rate of progression of liver injury in adults with Pi-ZZ Alpha-1 Antitrypsin Deficiency.
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Procedure: Liver Biopsy (Biopsy Group Only)
A percutaneous (needle) liver biopsy will be performed on subjects in the Liver Biopsy Group, in Year 1 and Year 5 of the study. |
Known Severe Liver Disease
Participants will provide samples of serum, plasma, and DNA at defined time points to determine what genetic and environmental modifiers and biomarkers are associated with severe clinical liver disease, such cirrhosis, portal hypertension and liver failure in adults with Pi-ZZ Alpha-1 Antitrypsin Deficiency.
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Post Liver Transplant
Participants will provide a DNA sample to determine what genetic and environmental modifiers are associated with the need for liver transplantation in adults with Pi-ZZ Alpha-1 Antitrypsin Deficiency.
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- The risk and rate of histologic liver injury progression, as measured by liver biopsy, over a 5-year period. [ Time Frame: Liver biopsy performed in Year 1 and Year 5 ]
- Calculated Model for End-stage Liver Disease score (MELD) [ Time Frame: Calculated at baseline and annually through year 5 ]
- Liver synthetic dysfunction defined by international normalized ratio (INR) > 1.3 or serum albumin < 3.2 gm/dL [ Time Frame: Measured at baseline and annually through year 5 ]
- Presence of ascites (or treatment for ascites) [ Time Frame: Assessed at baseline and annually through year 5 ]
- Development of complications of portal hypertension (e.g., variceal hemorrhage) [ Time Frame: Assessed at baseline and annually through year 5 ]
- Jaundice (total serum bilirubin >2.0 mg/dl) [ Time Frame: Measured at baseline and annually through year 5 ]
- Liver transplantation [ Time Frame: Assessed annually through year 5 ]
- Listing for liver transplantation [ Time Frame: Assessed at baseline and annually through year 5 ]
- Health related quality of life [ Time Frame: Measured at baseline and annually through year 5 ]
- FEV1 % of Predicted [ Time Frame: Collected at baseline and annually through year 5 ]
- Death [ Time Frame: Collected annually through year 5 ]
Biospecimen Retention: Samples With DNA

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
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 |
Liver Biopsy Group:
Inclusion Criteria
- Adults (≥ 18 years of age), with Alpha-1 Antitrypsin Deficiency
- Documented evidence Pi-ZZ phenotype or genotype
- Both genders, all races and ethnic groups
- Willingness to be followed for up to 5 years
Exclusion Criteria:
- Evidence of advanced liver disease defined by Child-Pugh Class B or C (score ≥ 7)
- Known advanced lung disease defined as forced expiratory volume at one second (FEV1) < 40 % of Predicted
- History of Organ Transplantation
- Known congenital or metabolic liver disease (e.g.: Wilson's, glycogen storage, cystic fibrosis)or iron overload as evidenced by ≥ Grade 3 iron staining on a previous liver biopsy
- Evidence of chronic hepatitis B (marked by the presence of HBsAg in serum) or Hepatitis C (marked by the presence of anti-hepatitis C virus (HCV) or HCV RNA in serum)
- Vascular disorders of the liver (e.g.: cardiac sclerosis, acute or chronic Budd-Chiari, hepatoportal sclerosis, peliosis)
- Known HIV positivity
- Diagnosis of malignancy within the last 5 years
- Active substance abuse, that in the opinion of the study investigator, would interfere with adherence to study requirements
- Concomitant severe underlying systemic illness or medical condition which in the opinion of the investigator, would make the patient unsuitable for the study or would interfere with completion of follow-up
- Inability to comply with the longitudinal follow-up as outlined in the protocol
- Failure of the participant to sign informed consent or Health Insurance Portability and Accountability Act (HIPAA) documents
Known Severe Liver Disease Group:
Inclusion Criteria
- Adults (≥ 18 years of age), with alpha-1-antitrypsin deficiency
- Documented evidence PI-ZZ phenotype or genotype
- Documented evidence of portal hypertension or evidence of advanced liver disease defined by Child-Pugh Class B or C (score ≥ 7), or previous liver biopsy with an Ishak Fibrosis Score ≥ 4
- Both genders, all races and ethnic groups
- Willingness to be followed for up to 5 years
Exclusion Criteria
- History of Organ Transplantation
- Known congenital or metabolic liver disease (e.g.: Wilson's, glycogen storage, cystic fibrosis) and iron overload as evidenced by ≥ Grade 3 iron staining on a previous liver biopsy
- Evidence of chronic hepatitis B (marked by the presence of HBsAg in serum) or Hepatitis C (marked by the presence of anti-HCV or HCV RNA in serum)
- Vascular disorders of the liver (e.g.: cardiac sclerosis, acute or chronic Budd-Chiari, hepatoportal sclerosis, peliosis)
- Known HIV positivity
- Diagnosis of malignancy within the last 5 years which in the opinion of the investigator, would make the patient's follow-up problematic or the results uninterpretable.
- Active substance abuse, that in the opinion of the study investigator, would interfere with adherence to study requirements
- Concomitant severe underlying systemic illness or medical condition which in the opinion of the investigator, would make the patient unsuitable for the study or would interfere with completion of follow-up
- Inability to comply with the longitudinal follow-up as outlined in the protocol
- Failure of the participant to sign informed consent or HIPAA documents.
Post Liver Transplant Group
Inclusion Criteria
- Adults (≥ 18 years of age), with alpha-1-antitrypsin deficiency
- Pre-transplant documented evidence of PI-ZZ phenotype or genotype
- Documented evidence of liver transplantation
- Both genders, all races and ethnic groups
Exclusion Criteria
- Active substance abuse, that in the opinion of the study investigator, would interfere with adherence to study requirements
- Concomitant severe underlying systemic illness or medical condition which in the opinion of the investigator, would make the patient unsuitable for the study or would interfere with completion of study requirements
- Failure of the participant to sign informed consent or HIPAA documents.

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): NCT02014415
United States, California | |
University of California | Recruiting |
San Diego, California, United States, 92103 | |
Contact: Lori Edge 858-246-5333 ledge@health.ucsd.edu | |
Principal Investigator: David A. Brenner, MD | |
Sub-Investigator: Rohit Loomba, MD, MHSc | |
United States, Massachusetts | |
Boston University School of Medicine | Recruiting |
Boston, Massachusetts, United States, 02118 | |
Contact: Mark Dodge 617-414-2968 mdodge1@bu.edu | |
Principal Investigator: Andrew Wilson, MD | |
United States, Missouri | |
Saint Louis University | Recruiting |
Saint Louis, Missouri, United States, 63104 | |
Contact: Jackie Cerkoski, RN, BSN 314-577-5611 jacqueline.cerkoski@health.slu.edu | |
Contact: Rosemary Nagy, RDN, LD, MBA 314-577-5608 rosemary.nagy@health.slu.edu | |
Sub-Investigator: Bruce R. Bacon, MD | |
Principal Investigator: Kamran Qureshi, MD |
Study Chair: | Jeffrey Teckman, MD | St. Louis University | |
Study Director: | Adam Wanner, MD | Alpha-1 Foundation | |
Principal Investigator: | David A. Brenner, MD | The University of California, San Diego | |
Principal Investigator: | Kamran Qureshi, MD | St. Louis University | |
Principal Investigator: | Andrew Wilson, MD | Boston University |
Responsible Party: | Jeffrey Teckman M.D., Professor of Pediatrics and Professor of Biochemistry and Molecular Biology, St. Louis University |
ClinicalTrials.gov Identifier: | NCT02014415 |
Other Study ID Numbers: |
A1F-SLU-7113 Alpha-1 Foundation ( Other Grant/Funding Number: A1F-SLU-7113 ) 22609 ( Other Identifier: Saint Louis University IRB ) |
First Posted: | December 18, 2013 Key Record Dates |
Last Update Posted: | February 15, 2022 |
Last Verified: | February 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Based on study group assignment, participants will be given a copy of their test results as follows: Liver Biopsy Group- liver biopsy pathology, diagnostic abdominal ultrasound, pulmonary function testing, and routine clinical laboratory testing. Known Severe Liver Disease Group- diagnostic abdominal ultrasound, pulmonary function testing, and routine clinical laboratory testing. Post Liver Transplant Group- pulmonary function testing. |
Alpha-1 AAT Deficiency AATD Liver |
Fibrosis Liver Transplant Cirrhosis |
Alpha 1-Antitrypsin Deficiency Liver Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases |
Genetic Diseases, Inborn Subcutaneous Emphysema Emphysema Pathologic Processes |