Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC)

This study is currently recruiting participants.
Verified October 2013 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00571272
First received: December 7, 2007
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

Cholestasis is a condition in which bile is not properly transported from the liver to the small intestine. Cholestasis can be caused by an array of childhood diseases, including the genetic diseases Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and progressive familial intrahepatic cholestasis (PFIC) or benign recurrent intrahepatic cholestasis(BRIC). This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.


Condition
Liver Diseases
Alagille Syndrome
Alpha 1-Antitrypsin Deficiency

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Demonstration of disease progression for each of the four cholestatic liver diseases of the study, including liver transplantation, death, growth failure, worsening liver function, and developmental complications of portal high blood pressure [ Time Frame: Measured at baseline and annually through year 10 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Jaundice (total serum bilirubin of greater than 2.0 mg/dl) [ Time Frame: Measured at baseline and annually through year 10 ] [ Designated as safety issue: No ]
  • Listing for liver transplantation [ Time Frame: Measured at baseline and annually through year 10 ] [ Designated as safety issue: No ]
  • Calculated Pediatric End-Stage Liver Disease (PELD) score for participants less than 12 years of age or Model for End-Stage Liver Disease (MELD) score for participants 12 years of age or older [ Time Frame: Measured at baseline and annually through year 10 ] [ Designated as safety issue: No ]
  • Health related quality of life [ Time Frame: Measured at baseline and annually through year 10 ] [ Designated as safety issue: No ]
  • Growth (length and weight Z-score) [ Time Frame: Measured at baseline and annually through year 10 ] [ Designated as safety issue: No ]
  • Bone mineral density (lumbar and spine total body) [ Time Frame: Measured at baseline in ALGS and PFIC/BRIC subjects ] [ Designated as safety issue: No ]
  • Presence of hearing loss (ALGS and PFIC) [ Time Frame: Measured at baseline ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood plasma and serum samples with DNA


Estimated Enrollment: 1150
Study Start Date: November 2007
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Infants less than 6 months old with a cholestatic liver disease who were initially enrolled into the Childhood Liver Disease Research and Education Network (ChiLDREN) Prospective Biliary Atresia Epidemiology study (PROBE study; P003)
2
Participants with a cholestatic liver disease who are between birth and 25 years old who were NOT initially enrolled into the Childhood Liver Disease Research and Education Network (ChiLDREN) Prospective Biliary Atresia Epidemiology study (PROBE study; P003)
3
Post-liver transplant participants with a cholestatic liver disease who are between 1 day and 25 years old. Affected parents of patients enrolled in the study are eligible for enrollment if they are 25 years old or less
4
A screening group of participants, birth through 25 years old, suspected of having ALGS, PFIC (or BRIC) or BAD, who do not meet complete enrollment criteria for Group 1, 2, or 3.BRIC)
5
Affected siblings (without evidence of liver disease) of Alpha-1 Antitrypsin Deficiency participants who are enrolled in LOGIC.

Detailed Description:

Cholestasis is a rare condition that involves a reduction or obstruction of bile flow from the liver to the small intestine. When bile flow is hindered, a waste product pigment called bilirubin can escape into the bloodstream and build up to harmful levels. This may lead to the easily recognizable cholestatic symptoms of jaundice, itching, and impaired growth and eventually to more serious health problems. Four rare genetic liver disorders— ALGS, a-1AT, bile acid synthesis and metabolism defects, and PFIC—account for about 20% to 30% of all infant cases of cholestasis. These four disorders compose a group of related diseases that can cause significant growth problems during childhood, serious liver problems, the need for liver transplantation, and potentially death. More research on these rare liver diseases is necessary to develop a scientific basis for improvement in diagnostic techniques and treatments. Current diagnostic procedures are complex, and the development of simpler diagnostic tests would facilitate early diagnosis and treatment. This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.

Participation in this study will last 10 years and will consist of a baseline visit and five annual follow-up visits. The study will enroll infants through adults 25 years of age who have, or are suspected of having, one of the four genetic cholestatic liver diseases. Individuals who are siblings of a-A1T aparticipants and have underlying disease with no evidence of liver involvement may also be enrolled. Study visits will involve review of clinical information, family history, and any clinically indicated treatments and their outcomes; a physical exam; laboratory tests; and radiologic and imaging evaluations. In addition to these standard of care evaluations, participants will undergo several special research evaluations, including quality of life questionnaires, neurodevelopmental evaluations, hearing exams, DEXA scanning (dual energy x-ray absorptiometry, liver histology studies, and collection of serum, plasma, urine, and blood for DNA or cell lines. Serum, plasma, urine, and blood for DNA or cell lines will also be collected from both biological parents and from affected siblings of participants with a-A1T or ALGS. Genetic testing will be performed using the collected specimens.

  Eligibility

Ages Eligible for Study:   up to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The study population will consist of 400 participants with Alagille syndrome, 400 with alpha-1 trypsin deficieny (of which up to 25 may be siblings of participants), 300 with PFIC (or BRIC), and 50 with bile acid synthesis defects.

Criteria

Inclusion Criteria:

  1. Children and young adults diagnosed with one of the four cholestatic diseases from birth through 25 years old.
  2. Siblings of participants with alpha-1-antitrypsin deficiency, who themselves have alpha-1-antitrypsin deficiency of liver disease.
  3. Both genders, all races and ethnic groups
  4. Participant meets the enrollment criteria for one of the four cholestatic liver diseases

Exclusion Criteria:

  1. Inability to comply with the longitudinal follow-up described below, or
  2. Failure of a family/patient to sign the informed consent document or the HIPAA medical record release form.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00571272

Contacts
Contact: Karen Jones 734-763-7738 ksjone@umich.edu
Contact: Beverley Marchant, BS, BS 734-615-3196 bevm@umich.edu

Locations
United States, California
Children's Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Catherine Goodhue, CPNP    323-361-4566    cgoodhue@chla.usc.edu   
Principal Investigator: Kasper Wang, MD         
University of California at San Francisco (UCSF) Recruiting
San Francisco, California, United States, 94143
Contact: Camille Langlois    415-476-1756    langloisc@peds.ucsf.edu   
Contact: Shannon Fleck    415-476-1539    flecks@peds.ucsf.edu   
Principal Investigator: Phillip Rosenthal, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Michelle Hite    720-777-4690    michelle.hite@childrenscolorado.org   
Contact: Todd Miller    720-777-5304    todd.miller@childrenscolorado.org   
Principal Investigator: Ronald J. Sokol, MD         
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Contact: Rita Tory    404-785-1467    rita.tory@choa.org   
Contact: Dana Hankerson-Dyson    404-785-6027    dana.hankerson-dyson@choa.org   
Principal Investigator: Saul Karpen, MD, PhD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Elizabeth Westfall    312-227-4558    ewestfall@luriechildrens.org   
Contact: Susan M. Kelly, RN, BSN    312-227-3523    skelly@luriechildrens.org   
Principal Investigator: Peter Whitington, MD         
United States, Indiana
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Beth Byam, RN    317-948-5803    ebyam@iupui.edu   
Contact: Cindy Sawyers    317-944-1421    clsawyer@iu.edu   
Principal Investigator: Jean Molleston, MD         
United States, Maryland
Johns Hopkins University Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Kim Pfeifer, BSN    410-614-8583    kfehily2@jhmi.edu   
Contact: Anita Osire    410- 614-1820    sosire1@jhmi.edu   
Principal Investigator: Kathleen Schwarz, MD         
United States, Missouri
Washington University School of Medicine/St. Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Kathleen Harris    314-747-5708    harris_k@kids.wustl.edu   
Contact: Stacy Postma    314-747-5931    postma_s@kids.wustl.edu   
Principal Investigator: Yumi Turmelle, MD         
St. Louis University - Cardinal Glennon Children's Medical Center Recruiting
St. Louis, Missouri, United States, 631104
Contact: Vikki Kociela, BSN, CCRC    314-577-5608    kocielav@slu.edu   
Principal Investigator: Jeff Teckman, MD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York City, New York, United States, 10029
Contact: Sheetal Ramnath    212-659-8046    sheetal.ramnath@mountsinai.org   
Principal Investigator: Ronen Arnon, MD         
United States, Ohio
Cincinnati's Children's Memorial Hospital Recruiting
Cincinnati, Ohio, United States, 60190
Contact: Julie Denlinger    513-636-7818    julie.denlinger@cchmc.org   
Contact: Andrea Ferris    513-803-0675    andrea.ferris@cchmc.org   
Principal Investigator: Jorge Bezerra, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jessi Erlichman    215-590-2525    erlichman@email.chop.edu   
Contact: Timothy Crisco    215-590-6853    criscit@email.chop.edu   
Principal Investigator: Kathy Loomes, MD         
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kathryn Bukauskas, RN    412-692-7703    kathryn.bukauskas@chp.edu   
Contact: Beverly Bernard, CRNP    412-692-5811    beverly.bernard@chp.edu   
Principal Investigator: Benjamin Shneider, MD         
United States, Texas
Baylor School of Medicine Active, not recruiting
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Melissa Young    206-987-1037    melissa.young@seattlechildrens.org   
Principal Investigator: Karen Murray, MD         
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Claudia Quammie    416-813-7654 ext 1594    claudia.quammie@sickkids.ca   
Contact: Kesley Hunt    416-813-7654 ext 201594    kelsey.hunt@sickkids.ca   
Principal Investigator: Vicky Ng, MD         
Sponsors and Collaborators
Investigators
Study Chair: Kathy Loomes, MD Children's Hospital of Philadelphia
Study Director: Ed Doo, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: John Magee, MD University of Michigan
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00571272     History of Changes
Other Study ID Numbers: RDCRN 6001
Study First Received: December 7, 2007
Last Updated: October 17, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Cholestatic Liver Disease
Cholestasis
Childhood Diseases
Genetic Diseases
Bile Acid Synthesis and Metabolism Defects
Progressive Familial Intrahepatic Cholestasis

Additional relevant MeSH terms:
Cholestasis
Cholestasis, Intrahepatic
Liver Diseases
Alagille Syndrome
Alpha 1-Antitrypsin Deficiency
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Lung Diseases
Respiratory Tract Diseases
Subcutaneous Emphysema
Emphysema
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014