Clinical Trial: Alpha-1 Antitrypsin Deficiency Adult Liver Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Alpha-1 Antitrypsin Deficiency Adult Clinical and Genetic Linkage Study

Brief Summary: 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.

Detailed Summary:

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:

  1. Liver Biopsy
  2. Known Severe Liver Disease - subjects not meeting Biopsy Group
    Sponsor: St. Louis University

    Current Primary Outcome: 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 ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • 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 ]


    Original Secondary Outcome: Same as current

    Information By: St. Louis University

    Dates:
    Date Received: December 12, 2013
    Date Started: December 2013
    Date Completion: August 2021
    Last Updated: January 3, 2017
    Last Verified: January 2017