Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC)
Information source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Liver Diseases; Alagille Syndrome; Alpha 1-Antitrypsin Deficiency
Phase: N/A
Status: Recruiting
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Official(s) and/or principal investigator(s): Kathy Loomes, MD, Study Chair, Affiliation: Children's Hospital of Philadelphia Ed Doo, MD, Study Director, Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) John Magee, MD, Principal Investigator, Affiliation: University of Michigan Robert Merion, MD, Principal Investigator, Affiliation: Arbor Research Collaborative for Health
Overall contact: Terese Howell, BS, CCRC, Phone: 734 369-9683, Email: thowell@umich.edu
Summary
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.
Clinical Details
Official title: Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis
Study design: Observational Model: Cohort, Time Perspective: Prospective
Primary outcome: 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
Secondary outcome: Jaundice (total serum bilirubin of greater than 2.0 mg/dl)Listing for liver transplantation 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 Health related quality of life Growth (length and weight Z-score) Bone mineral density (lumbar and spine total body) Presence of hearing loss (ALGS and PFIC)
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
Minimum age: N/A.
Maximum age: 25 Years.
Gender(s): Both.
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.
Locations and Contacts
Terese Howell, BS, CCRC, Phone: 734 369-9683, Email: thowell@umich.edu
Children's Hospital of Los Angeles, Los Angeles, California 90027, United States; Recruiting Catherine Goodhue, CPNP, Phone: 323-361-4566, Email: cgoodhue@chla.usc.edu Kasper Wang, MD, Principal Investigator Nanda Kerker, MD, Sub-Investigator Sonia Michail, MD, Sub-Investigator Danny Thomas, MD, Sub-Investigator
University of California at San Francisco (UCSF), San Francisco, California 94143, United States; Active, not recruiting
Children's Hospital Colorado, Aurora, Colorado 80045, United States; Recruiting Michelle Hite, Phone: 720-777-4690, Email: michelle.hite@childrenscolorado.org Todd Miller, Phone: 720-777-5304, Email: todd.miller@childrenscolorado.org Ronald J. Sokol, MD, Principal Investigator Cara Mack, MD, Sub-Investigator Michael Narkewicz, MD, Sub-Investigator Frederick Suchy, MD, Sub-Investigator Shikha Sundaram, MD, Sub-Investigator
Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States; Recruiting Rita Tory, Phone: 404-785-1467, Email: rita.tory@choa.org Dana Hankerson-Dyson, Phone: 404-785-6027, Email: dana.hankerson-dyson@choa.org Saul Karpen, MD, PhD, Principal Investigator Nitika Gupta, MD, Sub-Investigator Rene Romero, MD, Sub-Investigator Miriam Vos, MD, MSPH, Sub-Investigator
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, United States; Recruiting Elizabeth Kaurs, Phone: 312-227-4558, Email: ekaurs@luriechildrens.org Susan M. Kelly, RN, BSN, Phone: 312-227-3523, Email: skelly@luriechildrens.org Peter Whitington, MD, Principal Investigator Estella Alonso, MD, Sub-Investigator Lee Bass, MD, Sub-Investigator
Riley Hospital for Children, Indianapolis, Indiana 46202, United States; Recruiting Ann Klipsch, RN, Phone: 317-944-9605, Email: aeye@iupui.edu Cindy Sawyers, Phone: 317-944-1421, Email: clsawyer@iupui.edu Jean Molleston, MD, Principal Investigator Molly Bozic, MD, Sub-Investigator
Johns Hopkins University Hospital, Baltimore, Maryland 21287, United States; Completed
St. Louis University - Cardinal Glennon Children's Medical Center, St. Louis, Missouri 631104, United States; Recruiting Vikki Kociela, BSN, CCRC, Phone: 314-577-5608, Email: kocielav@slu.edu Jeff Teckman, MD, Principal Investigator
Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, Missouri 63110, United States; Completed
Mount Sinai School of Medicine, New York City, New York 10029, United States; Completed
Cincinnati's Children's Memorial Hospital, Cincinnati, Ohio 60190, United States; Recruiting Julie Denlinger, Phone: 513-636-7818, Email: julie.denlinger@cchmc.org Andrea Ferris, Phone: 513-803-0675, Email: andrea.ferris@cchmc.org Jorge Bezerra, MD, Principal Investigator James Heubi, MD, Sub-Investigator Alexander Miethke, MD, Sub-Investigator Joseph Palermo, MD, Sub-Investigator
The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; Recruiting Claudia Quammie, Phone: 416-813-7654, Ext: 201594, Email: claudia.quammie@sickkids.ca Kesley Hunt, Phone: 416-813-7654, Ext: 201594, Email: kelsey.hunt@sickkids.ca Vicky Ng, MD, Sub-Investigator Binita Kamath, MD, Principal Investigator
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting Jessi Erlichman, Phone: 215-590-2525, Email: erlichman@email.chop.edu Lindsay Brown, Phone: 267-426-0970, Email: brownL7@email.chop.edu Kathy Loomes, MD, Principal Investigator David Piccoli, MD, Sub-Investigator Elizabeth Rand, MD, Sub-Investigator
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting Kathryn Bukauskas, RN, Phone: 412-692-7703, Email: kathryn.bukauskas@chp.edu Madeline Schulte, Phone: 412-692-5811, Email: madeline.schulte@chp.edu Benjamin Shneider, MD, Principal Investigator Robert Squires, MD, Sub-Investigator Veena Venkat, MD, Sub-Investigator
Baylor School of Medicine, Houston, Texas 77030, United States; Active, not recruiting
Seattle Children's Hospital, Seattle, Washington 98105, United States; Recruiting Melissa Young, Phone: 206-987-1037, Email: melissa.young@seattlechildrens.org Kara Cooper, Phone: 206-987-4636, Email: kara.cooper@seattlechildrens.org Karen Murray, MD, Principal Investigator Simon Horslen, MD, Sub-Investigator Evelyn Shu, MD, Sub-Investigator
Additional Information
Childhood Liver Disease Research and Education Network (ChiLDREN) website
Starting date: November 2007
Last updated: April 15, 2015
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