Clinical trial NCT02922751: FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE)
Official title: Childhood Liver Disease Research Network (ChiLDReN): FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE) Study Protocol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Biliary Atresia
Alagille Syndrome
Alpha1 Anti-Trypsin Deficiency
Portal Hypertension
Liver Fibrosis
Cholestasis
Keywords: transient elastography
pediatric liver disease
biliary atresia
Alagille Syndrome
Alpha1 Anti-Trypsin Deficiency
liver fibrosis
cholestasis
Lead sponsor: Arbor Research Collaborative for Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2016-10-04
Enrollment: 552
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All children with an established diagnosis of BA (excluding those with known situs inversus or polysplenia/asplenia), who are actively followed at participating ChiLDReN sites and enrolled in PROBE or BASIC will be eligible for the trial. In addition, all children with A1AT or ALGS actively followed at one of these sites and enrolled in LOGIC will also be eligible.

Brief summary: Noninvasive monitoring of liver fibrosis is an unmet need within the clinical management of pediatric chronic liver disease. While liver biopsy is often used in the initial diagnostic evaluation, subsequent biopsies are rarely performed because of inherent invasiveness and risks. This study will evaluate the role of non-invasive FibroScan™ technology to detect and quantify liver fibrosis.

Detailed description: Noninvasive monitoring of liver fibrosis is an unmet and critical need within the clinical management of children with chronic liver disease. While liver biopsy is often used in the initial diagnostic evaluation of children with liver disease, subsequent surveillance liver biopsy is rarely performed in children because of its inherent invasiveness and risks. Therefore, our understanding of the natural history of fibrosis progression in children is limited. The patchy nature of fibrosis in many important pediatric liver diseases \[e.g. biliary atresia (BA) and cystic fibrosis liver disease (CFLD)\] limits the utility of sequential liver biopsy even if it were to be employed in clinical practice in pediatrics. Thus, non-invasive means of assessing liver fibrosis throughout the liver would be highly desirable and clinically useful in pediatric hepatology. ChiLDReN is poised and uniquely qualified to conduct a comprehensive longitudinal assessment of the utility of FibroScan™-specific elastography, liver stiffness measurement (LSM) as a measure of hepatic fibrosis in children with serious chronic cholestatic liver disease.

Eligibility criteria: Inclusion Criteria:

* Age less than 21 years at the time of enrollment
* Participants enrolled in a ChiLDReN based prospective observational cohort study (PROBE, BASIC, or LOGIC)
* Willingness and ability to participate in the study for up to 24 months
* One of the following three diagnoses

  * Biliary atresia per ChiLDReN criteria or,
  * Alpha-1 antitrypsin deficiency (PiZZ or SZ) or,
  * Alagille Syndrome per ChiLDReN criteria

Exclusion Criteria:

* BA with known situs inversus or polysplenia/asplenia
* Presence of clinically significant ascites detected on physical examination
* Open wound near expected FibroScan probe application site
* Use of implantable active medical device such as a pacemaker or defibrillator
* Known pregnancy
* Prior liver transplant
* Unable or unwilling to give informed consent or assent

Primary outcomes:
measure: Compare the distribution of LSM at enrollment between participants with and without portal hypertension
timeFrame: Enrollment
Secondary outcomes:
measure: Change in Liver Stiffness Measurement (LSM) obtained via transient elastography from baseline to LSM at the Year 1 and Year 2 visits in participants with biliary atresia (BA).
timeFrame: Baseline, Year 1 Visit, Year 2 Visit
measure: Number of participants in whom a valid FibroScan™ LSM can be obtained
timeFrame: Baseline, Year 1 Visit, Year 2 Visit
measure: FibroScan™ LSM values at enrollment and conventional laboratory determinants of liver disease ((Pediatric End Stage Liver Disease (PELD) and APRI (Aspartate Aminotransferase (AST) to Platelet Ratio Index)).
timeFrame: Baseline
Other outcomes:
measure: Change from LSM Measurement obtained via transient elastography from baseline, to LSM at the Year 1 and Year 2 visits in participants with A1AT and ALGS
timeFrame: Baseline, Year 1, and Year 2 Visits in children with A2AT, ALGS, and BA.
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco (UCSF)
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta (Emory University)
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Cincinnati
country: United States
facility: Cincinnati Children's Memorial Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital (Baylor College of Medicine)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Baylor College of Medicine
name: Benjamin Shneider, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Ed Doo, MD
role: STUDY_DIRECTOR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Averell Sherker, MD
role: STUDY_DIRECTOR
affiliation: University of Michigan Medical Center, Ann Arbor
name: John Magee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arbor Research Collaborative of Health
name: Lisa Henn, PhD
role: PRINCIPAL_INVESTIGATOR
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citation: Kim S, Kang Y, Lee MJ, Kim MJ, Han SJ, Koh H. Points to be considered when applying FibroScan S probe in children with biliary atresia. J Pediatr Gastroenterol Nutr. 2014 Nov;59(5):624-8. doi: 10.1097/MPG.0000000000000489.