FibroScan™ in Pediatric Cholestatic Liver Disease Study Protocol (FORCE)
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| ClinicalTrials.gov Identifier: NCT02922751 |
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Recruitment Status :
Enrolling by invitation
First Posted : October 4, 2016
Last Update Posted : February 19, 2018
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Sponsor:
Arbor Research Collaborative for Health
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Arbor Research Collaborative for Health
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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) |
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.
| Study Type : | Observational |
| Estimated Enrollment : | 450 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 2019 |
| Estimated Study Completion Date : | September 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Liver Diseases
| Group/Cohort | Intervention/treatment |
|---|---|
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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).
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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 :
- 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 :
- 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.
- 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.
- 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 Outcome Measures:
- 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 and ALGS. ]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
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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.
Criteria
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
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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 ClinicalTrials.gov identifier (NCT number): NCT02922751
Locations
| 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 | |
| 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 at Pittsburgh | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| United States, Texas | |
| Texas Children's Hospital | |
| 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)
Investigators
| 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) |
Additional Information:
Publications:
Keywords provided by Arbor Research Collaborative for Health:
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transient elastography pediatric liver disease biliary atresia Alagille Syndrome |
Alpha1 Anti-Trypsin Deficiency liver fibrosis cholestasis |
Additional relevant MeSH terms:
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Fibrosis Liver Diseases Hypertension, Portal Liver Cirrhosis Cholestasis Biliary Atresia Alagille Syndrome Alpha 1-Antitrypsin Deficiency Pathologic Processes Digestive System Diseases Bile Duct Diseases Biliary Tract Diseases Digestive System Abnormalities Congenital Abnormalities Cholestasis, Intrahepatic |
Heart Defects, Congenital Cardiovascular Abnormalities Cardiovascular Diseases Abnormalities, Multiple Genetic Diseases, Inborn Lung Diseases Respiratory Tract Diseases Subcutaneous Emphysema Emphysema Liver Extracts Alpha 1-Antitrypsin Hematinics Trypsin Inhibitors Serine Proteinase Inhibitors Protease Inhibitors |