FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE)

NCT02922751 | Completed DMC

• 18 other identifiers: FORCE Study - ChiLDReN NetworkU01DK103149U01DK103140U01DK103135U01DK084575U01DK084538U01DK084536U01DK062503U01DK062500U01DK062497U01DK062481U01DK062470U01DK062466U01DK062456U01DK062453U01DK062452U01DK062445U01DK062436
• Study Type: observational
• Target: 552
• Locations: 2 countries
• Sites: 13

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.

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

Outcome Measures

Primary Outcomes (1)

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

  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

  Enrollment

Secondary Outcomes (3)

• 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).

  Baseline, Year 1 Visit, Year 2 Visit

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

  Baseline, Year 1 Visit, Year 2 Visit

• 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)).

  Baseline

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

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

Study Arms (1)

All Subjects

All subjects will be recruited from the Children parent studies: LOGIC (NCT00571272), BASIC (NCT00345553) and PROBE (NCT00061828) and will undergo Liver Stiffness Measurement (LSM). Subjects in these studies have one or more of the following conditions: biliary atresia (BA), Alpha1 Anti-trypsin Deficiency (A1AT) or Alagille Syndrome (ALGS).

Other: Liver Stiffness Measurement (LSM)

Interventions

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.

Also known as: FibroScan™

All Subjects

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (13)

Children's Hospital 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

Cincinnati Children's Memorial Hospital

Cincinnati, Ohio, 60190, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Children's Hospital (Baylor College 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

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (14)

• Pinzani M, Macias-Barragan J. Update on the pathophysiology of liver fibrosis. Expert Rev Gastroenterol Hepatol. 2010 Aug;4(4):459-72. doi: 10.1586/egh.10.47.

  PMID: 20678019 BACKGROUND

• Trautwein C, Friedman SL, Schuppan D, Pinzani M. Hepatic fibrosis: Concept to treatment. J Hepatol. 2015 Apr;62(1 Suppl):S15-24. doi: 10.1016/j.jhep.2015.02.039.

  PMID: 25920084 BACKGROUND

• Shneider BL, Abel B, Haber B, Karpen SJ, Magee JC, Romero R, Schwarz K, Bass LM, Kerkar N, Miethke AG, Rosenthal P, Turmelle Y, Robuck PR, Sokol RJ; Childhood Liver Disease Research and Education Network. Portal hypertension in children and young adults with biliary atresia. J Pediatr Gastroenterol Nutr. 2012 Nov;55(5):567-73. doi: 10.1097/MPG.0b013e31826eb0cf.

  PMID: 22903006 BACKGROUND

• 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 BACKGROUND

• Bonis PA, Friedman SL, Kaplan MM. Is liver fibrosis reversible? N Engl J Med. 2001 Feb 8;344(6):452-4. doi: 10.1056/NEJM200102083440610. No abstract available.

  PMID: 11172184 BACKGROUND

• Ozaslan E. Drug-induced autoimmune hepatitis: an easily reversible type of liver fibrosis? Hepatology. 2011 Jan;53(1):370. doi: 10.1002/hep.23858. Epub 2010 Jul 29. No abstract available.

  PMID: 20848612 BACKGROUND

• Saleh HA, Abu-Rashed AH. Liver biopsy remains the gold standard for evaluation of chronic hepatitis and fibrosis. J Gastrointestin Liver Dis. 2007 Dec;16(4):425-6. No abstract available.

  PMID: 18193125 BACKGROUND

• Huang JF, Hsieh MY, Dai CY, Hou NJ, Lee LP, Lin ZY, Chen SC, Wang LY, Hsieh MY, Chang WY, Yu ML, Chuang WL. The incidence and risks of liver biopsy in non-cirrhotic patients: An evaluation of 3806 biopsies. Gut. 2007 May;56(5):736-7. doi: 10.1136/gut.2006.115410. No abstract available.

  PMID: 17440193 BACKGROUND

• Falck-Ytter Y, McCullough AJ. The risks of percutaneous liver biopsy. Hepatology. 2001 Mar;33(3):764. doi: 10.1053/jhep.2001.0103303le01. No abstract available.

  PMID: 11230761 BACKGROUND

• Westheim BH, Ostensen AB, Aagenaes I, Sanengen T, Almaas R. Evaluation of risk factors for bleeding after liver biopsy in children. J Pediatr Gastroenterol Nutr. 2012 Jul;55(1):82-7. doi: 10.1097/MPG.0b013e318249c12a.

  PMID: 22249806 BACKGROUND

• El-Shabrawi MH, El-Karaksy HM, Okahsa SH, Kamal NM, El-Batran G, Badr KA. Outpatient blind percutaneous liver biopsy in infants and children: is it safe? Saudi J Gastroenterol. 2012 Jan-Feb;18(1):26-33. doi: 10.4103/1319-3767.91735.

  PMID: 22249089 BACKGROUND

• Lachaux A, Le Gall C, Chambon M, Regnier F, Loras-Duclaux I, Bouvier R, Pinzaru M, Stamm D, Hermier M. Complications of percutaneous liver biopsy in infants and children. Eur J Pediatr. 1995 Aug;154(8):621-3. doi: 10.1007/BF02079063.

  PMID: 7588960 BACKGROUND

• Castera L, Bernard PH, Le Bail B, Foucher J, Trimoulet P, Merrouche W, Couzigou P, de Ledinghen V. Transient elastography and biomarkers for liver fibrosis assessment and follow-up of inactive hepatitis B carriers. Aliment Pharmacol Ther. 2011 Feb;33(4):455-65. doi: 10.1111/j.1365-2036.2010.04547.x.

  PMID: 21235598 BACKGROUND

• 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.

  PMID: 25003372 BACKGROUND

Related Links

• Childhood Liver Disease Research Network (ChiLDReN) website

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma and serum

MeSH Terms

Conditions

Biliary Atresia; Alagille Syndrome; alpha 1-Antitrypsin Deficiency; Hypertension, Portal; Liver Cirrhosis; Cholestasis

Condition Hierarchy (Ancestors)

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

Study Officials

• Benjamin Shneider, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Ed Doo, MD

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

  STUDY DIRECTOR

• Averell Sherker, MD

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

  STUDY DIRECTOR

• John Magee, MD

  University of Michigan Medical Center, Ann Arbor

  PRINCIPAL INVESTIGATOR

• Lisa Henn, PhD

  Arbor Research Collaborative of Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: October 4, 2016
• Study Start: November 16, 2016
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (12)