Alpha-1 Antitrypsin Deficiency Adult Liver Study
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.
|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|
- 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 ]
- 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.
|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)|
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02014415
|Contact: Rosemary Nagy, MBA, RD, LD||314-977-9350||Rnagy@slu.edu|
|Contact: Jackie Cerkoski, RN, BSNfirstname.lastname@example.org|
|United States, California|
|University of California||Recruiting|
|San Diego, California, United States, 92103|
|Contact: Phirum Nguyen 619-471-0774 email@example.com|
|Principal Investigator: David A. Brenner, MD|
|Sub-Investigator: Rohit Loomba, MD, MHSc|
|United States, Florida|
|University of Florida||Not yet recruiting|
|Gainesville, Florida, United States, 32610|
|Contact: Tracie L. Kurtz, RN 866-229-6313 firstname.lastname@example.org|
|Contact: Angie Bauer, BSN, RN 352-273-9512 email@example.com|
|Principal Investigator: David R. Nelson, MD|
|Sub-Investigator: Virginia Nelson, MD|
|United States, Missouri|
|Saint Louis University||Recruiting|
|Saint Louis, Missouri, United States, 63104|
|Contact: Jackie Cerkoski, RN, BSN 314-977-5239 firstname.lastname@example.org|
|Contact: Rosemary Nagy, MBA, RD, LD 314-977-9350 Rnagy@slu.edu|
|Principal Investigator: Adrian M. Di Bisceglie, MD, FACP|
|Sub-Investigator: Bruce R. Bacon, 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:||Adrian M. Di Bisceglie, MD, FACP||St. Louis University|
|Principal Investigator:||David R. Nelson, MD||The University of Florida, Gainesville|