Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)

Liver Diseases Clinical Trial

— LOGIC  

Official title:

Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00571272
• Other study ID #: LOGIC Study - ChiLDReN Network
• Secondary ID: U01DK103149U01DK
• Status: Recruiting
• Start date: November 30, 2007
• Est. completion date: May 2024

Study information

• Verified date: October 2023
• Source: Arbor Research Collaborative for Health
• Contact: Terese A Howell, BS, CCRC
• Phone: 734-476-5340
• Email: terri.howell[@]arborresearch.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1675
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alagille Syndrome
• Alpha 1-Antitrypsin Deficiency
• Cholestasis
• Cholestasis, Intrahepatic
• Liver Diseases

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	Children's Healthcare of Atlanta - Emory University	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University Hospital	Baltimore	Maryland
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati's Children's Memorial Hospital	Cincinnati	Ohio
United States	Baylor School of Medicine	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Mount Sinai School of Medicine	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	St. Louis University - Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine/St. Louis Children's Hospital	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of California at San Francisco (UCSF)	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Arbor Research Collaborative for Health	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Jaundice (total serum bilirubin of greater than 2.0 mg/dl)		Measured at baseline and annually through year 10
Secondary	Listing for liver transplantation		Measured at baseline and annually through year 10
Secondary	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
Secondary	Health related quality of life		Measured at baseline and annually through year 10
Secondary	Growth (length and weight Z-score)		Measured at baseline and annually through year 10
Secondary	Bone mineral density (lumbar and spine total body)		Measured at baseline in ALGS and PFIC/BRIC subjects
Secondary	Presence of hearing loss (ALGS and PFIC)		Measured at baseline

External Links

•   Childhood Liver Disease Research Network (ChiLDReN) website