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Trial record 2 of 2 for:    NCT00571272

FibroScan™ in Pediatric Cholestatic Liver Disease (FORCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02922751
Recruitment Status : Active, not recruiting
First Posted : October 4, 2016
Last Update Posted : August 7, 2019
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Arbor Research Collaborative for Health

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.

Condition or disease Intervention/treatment
Biliary Atresia Alagille Syndrome Alpha1 Anti-Trypsin Deficiency Portal Hypertension Liver Fibrosis Cholestasis Other: Liver Stiffness Measurement (LSM)

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.

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Study Type : Observational
Actual Enrollment : 458 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Childhood Liver Disease Research Network (ChiLDReN): FibroScan™ in Pediatric Cholestatic Liver Disease Study Protocol
Actual Study Start Date : November 16, 2016
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : December 2022

Group/Cohort Intervention/treatment
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)
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 Name: FibroScan™

Primary Outcome Measures :
  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 Outcome Measures :
  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) []

    APRI is calculated as

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

Other Outcome Measures:
  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.

Biospecimen Retention:   Samples Without DNA
Plasma and serum

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02922751

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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
University of California at San Francisco (UCSF)
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Healthcare of Atlanta (Emory University)
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Ohio
Cincinnati Children's Memorial Hospital
Cincinnati, Ohio, United States, 60190
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Texas Children's Hospital (Baylor College of Medicine)
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84113
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Arbor Research Collaborative for Health
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Benjamin Shneider, MD Texas Children's Hospital
Study Director: 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)
Principal Investigator: John Magee, MD University of Michigan Medical Center, Ann Arbor
Principal Investigator: Robert Merion, MD Arbor Research Collaborative of Health

Additional Information:

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Responsible Party: Arbor Research Collaborative for Health Identifier: NCT02922751     History of Changes
Other Study ID Numbers: FORCE Study - ChiLDReN Network
U01DK103149 ( U.S. NIH Grant/Contract )
U01DK103140 ( U.S. NIH Grant/Contract )
U01DK103135 ( U.S. NIH Grant/Contract )
U01DK084575 ( U.S. NIH Grant/Contract )
U01DK084538 ( U.S. NIH Grant/Contract )
U01DK084536 ( U.S. NIH Grant/Contract )
U01DK062503 ( U.S. NIH Grant/Contract )
U01DK062500 ( U.S. NIH Grant/Contract )
U01DK062497 ( U.S. NIH Grant/Contract )
U01DK062481 ( U.S. NIH Grant/Contract )
U01DK062470 ( U.S. NIH Grant/Contract )
U01DK062466 ( U.S. NIH Grant/Contract )
U01DK062456 ( U.S. NIH Grant/Contract )
U01DK062453 ( U.S. NIH Grant/Contract )
U01DK062452 ( U.S. NIH Grant/Contract )
U01DK062445 ( U.S. NIH Grant/Contract )
U01DK062436 ( U.S. NIH Grant/Contract )
First Posted: October 4, 2016    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified data will be shared via the NIDDK's Data Repository.
Keywords provided by Arbor Research Collaborative for Health:
transient elastography
pediatric liver disease
biliary atresia
Alagille Syndrome
Alpha1 Anti-Trypsin Deficiency
liver fibrosis
Additional relevant MeSH terms:
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Liver Diseases
Liver Cirrhosis
Hypertension, Portal
Biliary Atresia
Alagille Syndrome
Alpha 1-Antitrypsin Deficiency
Pathologic Processes
Cardiovascular Diseases
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Abnormalities
Congenital Abnormalities
Cholestasis, Intrahepatic
Heart Defects, Congenital
Cardiovascular Abnormalities
Abnormalities, Multiple
Genetic Diseases, Inborn
Lung Diseases
Respiratory Tract Diseases
Subcutaneous Emphysema
Liver Extracts
Alpha 1-Antitrypsin
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors