FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE)

Portal Hypertension Clinical Trial

— FORCE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02922751
• Other study ID #: FORCE Study - ChiLDReN Network
• Secondary ID: U01DK103149U01DK
• Status: Active, not recruiting
• Start date: November 16, 2016
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Arbor Research Collaborative for Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 552
• Est. completion date: December 2024
• Est. primary completion date: December 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Alagille Syndrome
• Alpha 1-Antitrypsin Deficiency
• Alpha1 Anti-Trypsin Deficiency
• Biliary Atresia
• Cholestasis
• Fibrosis
• Hypertension, Portal
• Liver Cirrhosis
• Liver Diseases
• Liver Fibrosis
• Portal Hypertension

Intervention

Other:
• Liver Stiffness Measurement (LSM)
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.

Locations

Country	Name	City	State
Canada	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	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Memorial Hospital	Cincinnati	Ohio
United States	Texas Children's Hospital (Baylor College of Medicine)	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
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, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Pediatr Gastroenterol Nutr. 2012 Aug;55(2):235. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	To prospectively explore changes in LSM over time by FibroScan™ in children with A1AT and ALGS.	Baseline, Year 1, and Year 2 Visits in children with A2AT, ALGS, and BA.
Primary	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	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).	The key secondary aim (Aim 2) compares the one- and two-year FibroScan™ values to those at enrollment in participants with BA.	Baseline, Year 1 Visit, Year 2 Visit
Secondary	Number of participants in whom a valid FibroScan™ LSM can be obtained	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.	Baseline, Year 1 Visit, Year 2 Visit
Secondary	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)).	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])	Baseline

External Links

•   Childhood Liver Disease Research Network (ChiLDReN) website