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NCT Number: NCT02922751

FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE)

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.

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Key information

Conditions

Biliary Atresia Abnormalities, Multiple Alagille Syndrome Alpha1 Anti-Trypsin Deficiency Bile Duct Diseases Biliary Tract Diseases Cardiovascular Abnormalities Cardiovascular Diseases Cholestasis Cholestasis, Intrahepatic Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Abnormalities Digestive System Diseases Emphysema Fibrosis Genetic Diseases, Inborn Heart Defects, Congenital Hypertension, Portal Liver Cirrhosis Liver Diseases Liver Fibrosis Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Portal Hypertension Respiratory Tract Diseases Subcutaneous Emphysema alpha 1-Antitrypsin Deficiency

Age range

Up to 21 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital for Sick Children, Toronto, Ontario, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Liver Stiffness Measurement (LSM)

Other

LSM will be measured via transient elastography utilizing the non-invasive FibroScan™ ultrasound device. LSM will be measured at Baseline, Year 1 and Year 2 visits.

Other names: FibroScan™

Primary outcomes

  1. Compare the distribution of LSM at enrollment between participants with and without portal hypertension

    Time frame: Enrollment

    A linear model will be fit to FibroScan™ values at enrollment to assess the impact of portal hypertension on LSM, controlling for important covariates such as age, gender, and race

Secondary outcomes

  1. 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).

    Time frame: Baseline, Year 1 Visit, Year 2 Visit

    The key secondary aim (Aim 2) compares the one- and two-year FibroScan™ values to those at enrollment in participants with BA.

  2. Number of participants in whom a valid FibroScan™ LSM can be obtained

    Time frame: Baseline, Year 1 Visit, Year 2 Visit

    The investigators will define two measures of the feasibility of FibroScans™ in the participant populations with a "technically possible" FibroScan™, defined as the number of subjects with at least 10 FibroScan™ measurements obtained divided by the number assessed. The proportion of subjects with FibroScans™ of "acceptable quality" is defined as the number of subjects with FibroScan™ LSM with the ratio of the interquartile range and median of the 10 measurements <30%, of which at least 6 are completed, divided by the number assessed. The proportions and their 95% confidence intervals will be provided using the Wald method; however, the Wilson-Score methods will be used if the sample sizes are small or the proportion is small for a disease group. We will perform separate analyses for subjects <2 years of age and for those >2 years of age.

  3. 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)).

    Time frame: Baseline

    The analysis will be limited to subjects for whom a PELD can be calculated (i.e., those for whom the individual components of the PELD score are available). Note that PELD will be calculated for all pediatric participants including those greater than 12 years of age. PELD is calculated as

    PELD = 4.80 x [ln serum bilirubin (mg/dL)] + 18.57 x [ln INR] - 6.87 x [ln albumin (g/dL)]

    + 4.36(<1 year old) + 6.67(growth failure) [www.unos.org]

    APRI is calculated as

    APRI = AST/upper limit of normal AST x 100 [U/L] Platelet Count (109/L) [U/L])

Other outcomes

  1. 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

    Time frame: Baseline, Year 1, and Year 2 Visits in children with A2AT, ALGS, and BA.

    To prospectively explore changes in LSM over time by FibroScan™ in children with A1AT and ALGS.

Sponsors and collaborators

Lead sponsor

Arbor Research Collaborative for Health

Other

Collaborators

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

Registry information

Official study title

Childhood Liver Disease Research Network (ChiLDReN): FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE) Study Protocol

Acronym: FORCE

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Oct 4, 2016
Registry last updated
Aug 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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