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 : January 18, 2018
|Condition or disease||Intervention/treatment|
|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|
|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 :||August 2020|
|Estimated Study Completion Date :||August 2021|
U.S. FDA Resources
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 (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.
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.
- 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
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: Phirum Nguyen 619-471-0774 email@example.com|
|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 firstname.lastname@example.org|
|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 email@example.com|
|Contact: Rosemary Nagy, RDN, LD, MBA 314-577-5608 firstname.lastname@example.org|
|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:||Andrew Wilson, MD||Boston University|