Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)

NCT00571272 | Suspended DMC

• 19 other identifiers: LOGIC Study - ChiLDReN NetworkU01DK103149U01DK103140U01DK103135U01DK084575U01DK084538U01DK084536U01DK062503U01DK062500U01DK062497U01DK062481U01DK062470U01DK062466U01DK062456U01DK062453U01DK062452U01DK062445U01DK062436U24DK062456
• Study Type: observational
• Target: 1,675
• Locations: 2 countries
• Sites: 17

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.

Conditions

Liver Diseases; Alagille Syndrome; Alpha 1-Antitrypsin Deficiency

Keywords

Cholestatic Liver Disease; Cholestasis; Childhood Diseases; Genetic Diseases; Bile Acid Synthesis and Metabolism Defects; Progressive Familial Intrahepatic Cholestasis

Outcome Measures

Primary Outcomes (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

  Measured at baseline and annually through year 10

Secondary Outcomes (7)

• Jaundice (total serum bilirubin of greater than 2.0 mg/dl)

  Measured at baseline and annually through year 10

• Listing for liver transplantation

  Measured at baseline and annually through year 10

• 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

  Measured at baseline and annually through year 10

• Health related quality of life

  Measured at baseline and annually through year 10

• Growth (length and weight Z-score)

  Measured at baseline and annually through year 10

Study Arms (4)

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

5

Affected siblings (without evidence of liver disease) of Alpha-1 Antitrypsin Deficiency participants who are enrolled in LOGIC.

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• Children and young adults diagnosed with one of the four cholestatic diseases from birth through 25 years old.
• Siblings of participants with alpha-1-antitrypsin deficiency, who are affected with alpha-1-antitrypsin deficiency, but have no evidence of liver disease.
• Both sexes, all races and ethnic groups.
• Participant meets the enrollment criteria for one of the four cholestatic liver diseases.
• Patient and/or parent/legal guardian have the ability to provide written informed consent for enrollment.

You may not qualify if:

• \. Inability to comply with the longitudinal follow-up described in the protocol.

Sponsors & Collaborators

• Arbor Research Collaborative for Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (17)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of California at San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta - Emory University

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University Hospital

Baltimore, Maryland, 21287, United States

Location

St. Louis University - Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine/St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Cincinnati's Children's Memorial Hospital

Cincinnati, Ohio, 60190, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Baylor School of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (3)

• Teckman J, Rosenthal P, Ignacio RV, Spino C, Bass LM, Horslen S, Wang K, Magee JC, Karpen S, Asai A, Molleston JP, Squires RH, Kamath BM, Guthery SL, Loomes KM, Shneider BL, Sokol RJ; ChiLDReN (Childhood Liver Disease Research Network). Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance. Hepatol Commun. 2023 Dec 7;7(12):e0345. doi: 10.1097/HC9.0000000000000345. eCollection 2023 Dec 1.

  PMID: 38055647 DERIVED

• Leung DH, Sorensen LG, Ye W, Hawthorne K, Ng VL, Loomes KM, Fredericks EM, Alonso EM, Heubi JE, Horslen SP, Karpen SJ, Molleston JP, Rosenthal P, Sokol RJ, Squires RH, Wang KS, Kamath BM, Magee JC; Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver. J Pediatr Gastroenterol Nutr. 2022 Jan 1;74(1):96-103. doi: 10.1097/MPG.0000000000003337.

  PMID: 34694263 DERIVED

• Teckman JH, Rosenthal P, Abel R, Bass LM, Michail S, Murray KF, Rudnick DA, Thomas DW, Spino C, Arnon R, Hertel PM, Heubi J, Kamath BM, Karnsakul W, Loomes KM, Magee JC, Molleston JP, Romero R, Shneider BL, Sherker AH, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Baseline Analysis of a Young alpha-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. J Pediatr Gastroenterol Nutr. 2015 Jul;61(1):94-101. doi: 10.1097/MPG.0000000000000753.

  PMID: 25651489 DERIVED

Related Links

• Childhood Liver Disease Research Network (ChiLDReN) website

MeSH Terms

Conditions

Liver Diseases; Alagille Syndrome; alpha 1-Antitrypsin Deficiency; Cholestasis; Genetic Diseases, Inborn; Cholestasis, progressive familial intrahepatic 1

Condition Hierarchy (Ancestors)

Digestive System Diseases; Cholestasis, Intrahepatic; Bile Duct Diseases; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kathleen Loomes, MD

  Children's Hospital of Philadelphia

  STUDY CHAIR

• Ed Doo, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

• John Magee, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Lisa Henn, PhD

  Arbor Research Collaborative for Health

  PRINCIPAL INVESTIGATOR

• Katrina Loh, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2007
• First Posted: December 11, 2007
• Study Start: November 30, 2007
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: October 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (16); CA (1)