FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE)

NCT ID: NCT02922751

Last Updated: 2024-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

552 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-11-16

Study Completion Date

2022-12-22

Brief Summary

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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

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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.

Conditions

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Biliary Atresia Alagille Syndrome Alpha1 Anti-Trypsin Deficiency Portal Hypertension Liver Fibrosis Cholestasis

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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).

Liver Stiffness Measurement (LSM)

Intervention Type 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.

Interventions

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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.

Intervention Type OTHER

Other Intervention Names

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FibroScan™

Eligibility Criteria

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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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role collaborator

Arbor Research Collaborative for Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Benjamin Shneider, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Ed Doo, MD

Role: STUDY_DIRECTOR

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

Averell Sherker, MD

Role: STUDY_DIRECTOR

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

John Magee, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Medical Center, Ann Arbor

Lisa Henn, PhD

Role: PRINCIPAL_INVESTIGATOR

Arbor Research Collaborative of Health

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

University of California at San Francisco (UCSF)

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's Healthcare of Atlanta (Emory University)

Atlanta, Georgia, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Cincinnati Children's Memorial Hospital

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Texas Children's Hospital (Baylor College of Medicine)

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 20678019 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25920084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22903006 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25651489 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11172184 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20848612 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18193125 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17440193 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11230761 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22249806 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22249089 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7588960 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21235598 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25003372 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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https://childrennetwork.org

Childhood Liver Disease Research Network (ChiLDReN) website

Other Identifiers

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U01DK103149

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK103140

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK103135

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK084575

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK084538

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK084536

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062503

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062500

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062497

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062481

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062470

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062466

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062456

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062445

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK062436

Identifier Type: NIH

Identifier Source: secondary_id

View Link

FORCE Study - ChiLDReN Network

Identifier Type: -

Identifier Source: org_study_id

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