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

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ClinicalTrials.gov Identifier: NCT00571272
Recruitment Status : Recruiting
First Posted : December 11, 2007
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Arbor Research Collaborative for Health

Brief 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.

Condition or disease
Liver Diseases Alagille Syndrome Alpha 1-Antitrypsin Deficiency

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 20 years and will consist of a baseline visit and 20 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 participants 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, liver histology studies, and collection of serum, plasma, urine, and blood for DNA. Serum, plasma, and blood for DNA 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.


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Study Type : Observational
Estimated Enrollment : 1675 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis
Study Start Date : November 2007
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024


Group/Cohort
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.



Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Jaundice (total serum bilirubin of greater than 2.0 mg/dl) [ Time Frame: Measured at baseline and annually through year 10 ]
  2. Listing for liver transplantation [ Time Frame: Measured at baseline and annually through year 10 ]
  3. 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 ]
  4. Health related quality of life [ Time Frame: Measured at baseline and annually through year 10 ]
  5. Growth (length and weight Z-score) [ Time Frame: Measured at baseline and annually through year 10 ]
  6. Bone mineral density (lumbar and spine total body) [ Time Frame: Measured at baseline in ALGS and PFIC/BRIC subjects ]
  7. Presence of hearing loss (ALGS and PFIC) [ Time Frame: Measured at baseline ]

Biospecimen Retention:   Samples With DNA
Blood plasma and serum samples with DNA


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00571272


Contacts
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Contact: Terese Howell, BS, CCRC 734-369-9683 terri.howell@arborresearch.org
Contact: Joanne Lord, BA, LPN, CCRC 734-369-9965 joanne.lord@arborresearch.org

Locations
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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         
Sub-Investigator: Nisreen Soufi, MD         
Sub-Investigator: Sonia Michail, MD         
Sub-Investigator: Danny Thomas, MD         
Sub-Investigator: Rohit Kohil, MD         
University of California at San Francisco (UCSF) Active, not recruiting
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Michelle Hite    720-777-4690    michelle.hite@childrenscolorado.org   
Contact: Matthew Steinbeiss    720-777-4800    matthew.steinbeiss@childrenscolorado.org   
Principal Investigator: Ronald J. Sokol, MD         
Sub-Investigator: Cara Mack, MD         
Sub-Investigator: Michael Narkewicz, MD         
Sub-Investigator: Shikha Sundaram, MD         
Sub-Investigator: Amy Feldman, MD         
Sub-Investigator: Dania Brigham, MD         
United States, Georgia
Children's Healthcare of Atlanta - Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jeanette McFall    404-785-0421    jeanette.mcfall@choa.org   
Principal Investigator: Saul Karpen, MD, PhD         
Sub-Investigator: Nitika Gupta, MD         
Sub-Investigator: Rene Romero, MD         
Sub-Investigator: Miriam Vos, MD, MSPH         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Susan M. Kelly, RN, BSN    312-227-3523    skelly@luriechildrens.org   
Contact: Mary Riordan, CCRP    312-227-4558    mriordan@luriechildrens.org   
Principal Investigator: Estella Alonso, MD         
Sub-Investigator: Lee Bass, MD         
United States, Indiana
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Ann Klipsch, RN    317-944-9605    aeye@iu.edu   
Contact: Cindy Sawyers    317-944-1421    clsawyer@iu.edu   
Principal Investigator: Jean Molleston, MD         
Sub-Investigator: Molly Bozic, MD         
United States, Maryland
Johns Hopkins University Hospital Completed
Baltimore, Maryland, United States, 21287
United States, Missouri
St. Louis University - Cardinal Glennon Children's Medical Center Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Shraddha Patel, Ph.D.    314-268-2700 ext 1095    shraddha.patel@health.slu.edu   
Principal Investigator: Jeff Teckman, MD         
Washington University School of Medicine/St. Louis Children's Hospital Completed
Saint Louis, Missouri, United States, 63110
United States, New York
Mount Sinai School of Medicine Completed
New York, New York, United States, 10029
United States, Ohio
Cincinnati's Children's Memorial Hospital Recruiting
Cincinnati, Ohio, United States, 60190
Contact: Julie Denlinger, RN, BSN    513-636-7818    julie.denlinger@cchmc.org   
Principal Investigator: Jorge Bezerra, MD         
Sub-Investigator: James Heubi, MD         
Sub-Investigator: Alexander Miethke, MD         
Sub-Investigator: Joseph Palermo, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jessi Erlichman, MPH    215-590-2525    erlichman@email.chop.edu   
Contact: Iraklis Petrof    267-426-8613    petrofi@email.chop.edu   
Principal Investigator: Kathy Loomes, MD         
Sub-Investigator: David Piccoli, MD         
Sub-Investigator: Elizabeth Rand, MD         
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Kathryn Bukauskas, RN, CCRC    412-692-7703    kathryn.bukauskas@chp.edu   
Contact: Adam Kufen, RN, CCRC    412-692-6558    adam.kufen@chp.edu   
Principal Investigator: Robert Squires, MD         
Sub-Investigator: Patrick Mckiernan, MD         
Sub-Investigator: James Squires, MD         
United States, Texas
Baylor School of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Laurel Cavallo    832-822-1053    laurel.cavallo@bcm.edu   
Contact: Cynthia Tsai, MPH    832-822-3634    ct2@bcm.edu   
Principal Investigator: Paula Hertel, MD         
Sub-Investigator: Benjamin Shneider, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Stephen Guthery, MD    801-213-3599    stephen.guthery@hsc.utah.edu   
Contact: Ann Rutherford    801-585-9495    ann.rutherford@hsc.utah.edu   
Principal Investigator: Stephen Guthery, MD         
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         
Sub-Investigator: Simon Horslen, MD         
Sub-Investigator: Evelyn Hsu, MD         
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Deepika Sharma    416-813-7654 ext 201594    deepika.sharma@sickkids.ca   
Contact: Claudia Quammie    416-813-7654 ext 201594    claudia.quammie@sickkids.ca   
Sub-Investigator: Vicky Ng, MD         
Principal Investigator: Binita Kamath, MD         
Sponsors and Collaborators
Arbor Research Collaborative for Health
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Study Chair: Kathleen 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
Principal Investigator: Robert Merion, MD Arbor Research Collaborative for Health
Study Director: Averell Sherker, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Arbor Research Collaborative for Health
ClinicalTrials.gov Identifier: NCT00571272     History of Changes
Other Study ID Numbers: LOGIC Study - ChiLDReN Network
U01DK103149 ( U.S. NIH Grant/Contract )
U01DK103140 ( U.S. NIH Grant/Contract )
U01DK103135 ( U.S. NIH Grant/Contract )
U01DK084575 ( U.S. NIH Grant/Contract )
U01DK084538 ( U.S. NIH Grant/Contract )
U01DK084536 ( U.S. NIH Grant/Contract )
U01DK062503 ( U.S. NIH Grant/Contract )
U01DK062500 ( U.S. NIH Grant/Contract )
U01DK062497 ( U.S. NIH Grant/Contract )
U01DK062481 ( U.S. NIH Grant/Contract )
U01DK062470 ( U.S. NIH Grant/Contract )
U01DK062466 ( U.S. NIH Grant/Contract )
U01DK062456 ( U.S. NIH Grant/Contract )
U01DK062453 ( U.S. NIH Grant/Contract )
U01DK062452 ( U.S. NIH Grant/Contract )
U01DK062445 ( U.S. NIH Grant/Contract )
U01DK062436 ( U.S. NIH Grant/Contract )
First Posted: December 11, 2007    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data will be transferred to NIDDK at the end of the study.

Keywords provided by Arbor Research Collaborative for Health:
Cholestatic Liver Disease
Cholestasis
Childhood Diseases
Genetic Diseases
Bile Acid Synthesis and Metabolism Defects
Progressive Familial Intrahepatic Cholestasis

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