Longitudinal Assessment of Transient Elastography in Cystic Fibrosis

To determine if transient elastography (TE), when combined with ultrasound (US) pattern characterization can improve the prediction of progression to a nodular pattern on US.

To confirm the feasibility of obtaining TE measurements in children with Cystic Fibrosis (CF) To prospectively assess whether TE data are associated with conventional laboratory markers of hepatic fibrosis To determine the variability of TE measurements taken at different sites in the same patient

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis Liver Disease
• Intervention / Treatment: Procedure: Transient Elastography (TE)

Detailed Description

A noninvasive assessment of hepatic fibrosis is desperately needed to advance the care of children with CF significant liver disease and to provide for measurements during clinical trials. That global assessment might serve as both a predictor/descriptor of disease course but also as a critical biomarker for clinical research. FibroScan® measurement of liver stiffness has great potential to fill this void. The underlying hypothesis of this proposal is that elastography in addition to US can improved the prediction of the development of a nodular liver on US and development of portal hypertension over time in children and young adults with CF.

• Study Type: Observational
• Enrollment (Actual): 141

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants enrolled in CFLD NET PUSH study in longitudinal follow up at centers with Fibroscan available (currently 8/11 centers) All racial and ethnic groups will be included.

Description

Inclusion Criteria:

• Participants enrolled in CFLD NET PUSH study in longitudinal follow up at centers with Fibroscan available (currently 8/11 centers)
• Entry criteria for that study were:
• CF as determined by sweat chloride >60 meq/l
• Pancreatic insufficiency
• Age 3-12 years old at entry

• For entry into the longitudinal follow up subjects were in one of two groups

  • A screening US pattern of nodular liver (CIR), heterogeneous increased echogenicity (HTG) or homogeneous increased echogenicity (HMG)
  • A screening US pattern of normal (NL) matched to a HTG subject (2 NL:1HTG) by age, center and pseudomonas status

Exclusion Criteria:

• Exited from the PUSH Study
• Unable / unwilling to sign consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Stiffness Measurement (LSM) obtained via transient elastography using FibroScanTM	Liver stiffness" quantifies liver fibrosis and is measured in kPa (median of 10 subsequent valid measurements and are deemed acceptable if the ratio of interquartile range and median is <30% and success rate is >60%, meaning 10 valid measurements are obtained within 16 attempts).	Baseline
Liver Stiffness Measurement (LSM) obtained via transient elastography using FibroScanTM	Liver stiffness" quantifies liver fibrosis and is measured in kPa (median of 10 subsequent valid measurements and are deemed acceptable if the ratio of interquartile range and median is <30% and success rate is >60%, meaning 10 valid measurements are obtained within 16 attempts).	Year 1
Liver Stiffness Measurement (LSM) obtained via transient elastography using FibroScanTM	Liver stiffness" quantifies liver fibrosis and is measured in kPa (median of 10 subsequent	Year 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver steatosis obtained via transient elastography	Controlled Attenuation Parameter (CAP)" quantifies liver steatosis and is measured in dB	Baseline, Year 1, Year 2
Comparison of liver stiffness and liver steatosis measurements at each time point to grayscale ultrasound grades	Grayscale ultrasound grades will be obtained from the parent study (PUSH: Clinical Trials: NCT01144507)	Baseline, Year 1 and Year 2
Comparison of liver stiffness and liver steatosis measurements at each time point to clinical findings of portal hypertension	Grayscale ultrasound grades will be obtained from the parent study (PUSH: Clinical Trials: NCT01144507)	Baseline, Year 1 and Year 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invalid measurements and success rate on liver stiffness and liver steatosis measurements		Baseline, Year 1 and Year 2
Inter quartile range (IQR) (kPa or dB/m) of all valid measurements within the examination	To reflect the dispersion of stiffness and steatosis	Baseline, Year 1 and Year 2
IQR/median ratio of all valid measurements within the examination	This quantity should remain as low as possible to ensure reliable results (goal < 30%)	Baseline, Year 1 and Year 2

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Cystic Fibrosis Foundation
• Investigators: 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)

Publications and helpful links

Helpful Links

• ChiLDReN Website

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): May 9, 2023
• Study Completion (Actual): May 9, 2023

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimated): December 23, 2016

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Pancreatic insufficiency; Transient Elastography; Cystic Fibrosis Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Liver Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: ELASTIC-CF; U01DK062456 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO