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Alpha-1 Antitrypsin Deficiency Adult Liver Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by St. Louis University
Alpha-1 Foundation
University of California
Boston University
University College, London
University of Massachusetts, Worcester
Information provided by (Responsible Party):
Jeffrey Teckman M.D., St. Louis University Identifier:
First received: December 12, 2013
Last updated: April 19, 2016
Last verified: April 2016
The investigators hypothesize that there is liver injury (inflammation, fibrosis, cirrhosis) in adults with Alpha-1 Antitrypsin Deficiency (AATD), which is asymptomatic, under-recognized, and undiagnosed. In addition, the investigators believe that the genetic and environmental factors that play an important role in the development of alpha-1 antitrypsin (AAT) liver disease, can be identified by comparing a cohort database of clinical disease information to linked biospecimen and DNA samples.

Condition Intervention
Alpha-1 Antitrypsin Deficiency
Procedure: Liver Biopsy

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: Alpha-1 Antitrypsin Deficiency Adult Clinical and Genetic Linkage Study

Resource links provided by NLM:

Further study details as provided by St. Louis University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Calculated Model for End-stage Liver Disease score (MELD) [ Time Frame: Calculated at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Presence of ascites (or treatment for ascites) [ Time Frame: Assessed at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • Development of complications of portal hypertension (e.g., variceal hemorrhage) [ Time Frame: Assessed at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • Jaundice (total serum bilirubin >2.0 mg/dl) [ Time Frame: Measured at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • Liver transplantation [ Time Frame: Assessed annually through year 5 ] [ Designated as safety issue: No ]
  • Listing for liver transplantation [ Time Frame: Assessed at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • Health related quality of life [ Time Frame: Measured at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • FEV1 % of Predicted [ Time Frame: Collected at baseline and annually through year 5 ] [ Designated as safety issue: No ]
  • Death [ Time Frame: Collected annually through year 5 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
Samples of liver tissue, serum, plasma, and blood for genetic testing (Induced Pluripotent Stem Cells (iPS cells), microRNA and DNA) will be collected from each subject at defined time points.

Estimated Enrollment: 100
Study Start Date: December 2013
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Pi-ZZ Adult Liver Biopsy Cohort
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.
Procedure: Liver Biopsy
Liver biopsy will be performed in Year 1 and Year 5 of the study.

Detailed Description:

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.

At least 100 adults with Pi-ZZ AATD will be enrolled in the study. 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 study will examine the natural history of liver disease by recording each participant's family history, medical history, current health, physical exam, laboratory test results, and medical treatment(s). Participants will complete several brief research questionnaires about their physical and mental health, diet, alcohol intake, smoking and secondhand smoke, environmental and occupational (work) exposures. Procedures performed for the research include liver biopsy, FibroScan testing, and the collection of serum, plasma and blood for routine laboratory and genetic testing (Induced Pluripotent Stem Cells (iPS cells), microRNA and DNA).

Participation in this study will last for 5 years and includes an enrollment visit and four annual follow-up visits. A liver biopsy is performed at enrollment and again in Year 5, to help the researchers learn what causes liver disease in some patients and how the liver disease progresses. Participants will be given copies of their routine laboratory test results and liver biopsy pathology reports to share with their primary care physician.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pi-ZZ AAT deficient adults with either no previous history of liver disease or Pi-ZZ adults with mild-moderate liver disease. Biologic family members who are also Pi-ZZ and ≥ 18 years of age, will be offered enrollment into the study. The purpose of including family members is to determine if the natural history of the liver disease is consistent in a given family.

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02014415

United States, California
University of California Recruiting
San Diego, California, United States, 92103
Contact: Phirum Nguyen    619-471-0774   
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   
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   
Contact: Jan Freebersyser, RN, BSN    314-977-5239   
Principal Investigator: Adrian M. Di Bisceglie, MD, FACP         
Sub-Investigator: Bruce R. Bacon, MD         
Sponsors and Collaborators
St. Louis University
Alpha-1 Foundation
University of California
Boston University
University College, London
University of Massachusetts, Worcester
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: Adrian M. Di Bisceglie, MD, FACP St. Louis University
Principal Investigator: Andrew Wilson, MD Boston University
  More Information

Responsible Party: Jeffrey Teckman M.D., Professor of Pediatrics and Professor of Biochemistry and Molecular Biology, St. Louis University Identifier: NCT02014415     History of Changes
Other Study ID Numbers: A1F-SLU-7113  Alpha-1 Foundation 
Study First Received: December 12, 2013
Last Updated: April 19, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Participants will be given a copy of their test results for the following: liver biopsy pathology, diagnostic abdominal ultrasound, pulmonary function testing, and routine clinical laboratory testing.

Keywords provided by St. Louis University:
AAT Deficiency

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Pathologic Processes
Liver Extracts
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on December 09, 2016