Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)

NCT ID: NCT00571272

Last Updated: 2025-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Total Enrollment

1675 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-11-30

Study Completion Date

2029-05-31

Brief Summary

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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.

Detailed Description

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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.

Participants who have been previously enrolled into this study will be followed for 20 years, until transplanted, or death. 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.

Conditions

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Liver Diseases Alagille Syndrome Alpha 1-Antitrypsin Deficiency

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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)

No interventions assigned to this group

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)

No interventions assigned to this group

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

No interventions assigned to this group

5

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

No interventions assigned to this group

Eligibility Criteria

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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 are affected with alpha-1-antitrypsin deficiency, but have no evidence of liver disease.
3. Both sexes, all races and ethnic groups.
4. Participant meets the enrollment criteria for one of the four cholestatic liver diseases.
5. Patient and/or parent/legal guardian have the ability to provide written informed consent for enrollment.

Exclusion Criteria

1\. Inability to comply with the longitudinal follow-up described in the protocol.
Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role collaborator

Arbor Research Collaborative for Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kathleen Loomes, MD

Role: STUDY_CHAIR

Children's Hospital of Philadelphia

Ed Doo, MD

Role: STUDY_DIRECTOR

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

John Magee, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Lisa Henn, PhD

Role: PRINCIPAL_INVESTIGATOR

Arbor Research Collaborative for Health

Katrina Loh, MD

Role: STUDY_DIRECTOR

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

Locations

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Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

University of California at San Francisco (UCSF)

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's Healthcare of Atlanta - Emory University

Atlanta, Georgia, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Johns Hopkins University Hospital

Baltimore, Maryland, United States

Site Status

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

St Louis, Missouri, United States

Site Status

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

St Louis, Missouri, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Cincinnati's Children's Memorial Hospital

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Baylor School of Medicine

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 38055647 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34694263 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25651489 (View on PubMed)

Related Links

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http://www.childrennetwork.org

Childhood Liver Disease Research Network (ChiLDReN) website

Other Identifiers

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U01DK103149

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK103140

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK103135

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK084575

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK084538

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK084536

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062503

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062500

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062497

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062481

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062470

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062466

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062456

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062445

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062436

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U24DK062456

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LOGIC Study - ChiLDReN Network

Identifier Type: -

Identifier Source: org_study_id

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