An Imaging-based Quantitative Biomarker Assay for NAFLD in Children

An Imaging-based Quantitative Biomarker Assay for Non-alcoholic Fatty Liver Disease (NAFLD) in Children: a Feasibility Study

This study will validate recently developed Magnetic Resonance Imaging (MRI) and Ultrasound (US) based methods for liver fat quantification in children with obesity and healthy range of body mass index (BMI).

Study Overview

• Status: Recruiting
• Conditions: NAFLD; NASH
• Intervention / Treatment: Device: Magnetic Resonance Imaging (MRI); Device: Ultrasound (US)

Detailed Description

The severity of the obesity epidemic in the U.S., particularly in Wisconsin, is alarming, with overall overweight or obesity rates of 35% in children. [Fryar 2020,] Obesity is a major risk factor for several comorbidities, one of the most common being non-alcoholic fatty liver disease (NAFLD, also denoted steatotic liver disease). The inflammatory state known as non-alcoholic steatohepatitis (NASH) may lead to fibrosis and, if left untreated, can lead to cirrhosis, liver failure, and cancer. For these reasons, there is enormous interest in effective interventions for weight loss and reversing NAFLD. A central challenge in the development of new interventions is the need for accurate and precise biomarkers to evaluate hepatic steatosis in children.

This pilot study focuses on demonstrating the feasibility of MRI and US based liver fat quantification in children and addresses technical challenges that may limit the performance of the proposed techniques in the population of interest through the following aims:

• Aim 1: Determine the bias and precision (repeatability) of emerging free-breathing MRI-based liver fat quantification in children with obesity and controls using current breath-held methods as a reference.
• Aim 2: Determine the precision (repeatability and reproducibility) of US-based biomarkers of liver steatosis with a focus on the impact of body wall thickness on the precision of the biomarkers.

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Gemma Gliori, MS; Phone Number: 608-262-7269; Email: ggliori@uwhealth.org
• Study Contact Backup: Name: Suzanne Hanson, BS; Phone Number: 608-262-7269; Email: shanson@uwhealth.org

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin, Madison
      • Contact: Gemma Gliori, MS; Phone Number: 608-262-7269; Email: ggliori@uwhealth.org
      • Contact: Suzanne Hanson, BS; Phone Number: 608-262-7269; Email: shanson@uwhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

1. 12 Children ages 10 - 14 years with BMI in the >95th percentile for age and sex
2. 12 Children ages 10 - 14 years with BMI < 85th percentile and >5th percentile for age and sex.

Description

Inclusion Criteria:

1. Age: 10 - 14years old
2. BMI: Case subjects: BMI>95th percentile for age and sex Healthy BMI volunteers: 5th ≤ BMI < 85th percentile for age and sex

Exclusion Criteria:

1. Children with contraindications to MRI.
2. Children who did not fast (verbally confirmed by children or guardian)
3. Pregnant

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Average or low BMI; Children with BMI under the 85th percentile for age and sex	Device: Magnetic Resonance Imaging (MRI); MRI procedures will include a 20-25 exam with periodic breath holds. The imaging series will be conducted twice to assess repeatability.; Device: Ultrasound (US); In each ultrasound exam, each participant will be scanned by two sonographers to evaluate inter-operator variability. Each exam will take approximately 60 minutes to complete. The imaging series will be conducted twice to assess repeatability.
High BMI; Children with BMI in the 95th percentile or higher for age and sex	Device: Magnetic Resonance Imaging (MRI); MRI procedures will include a 20-25 exam with periodic breath holds. The imaging series will be conducted twice to assess repeatability.; Device: Ultrasound (US); In each ultrasound exam, each participant will be scanned by two sonographers to evaluate inter-operator variability. Each exam will take approximately 60 minutes to complete. The imaging series will be conducted twice to assess repeatability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI	Validate and confirm the reliability of a recently developed free-breathing CSE-based PDFF mapping method in children with high and average/low BMI for age and sex. Bias and precision will be determined for each segment. Bias will be measured relative to the reference IDEAL IQ obtained in a 20-second breath-hold. In those subjects unable to hold their breath for 20 seconds, but able to hold their breath for 10 seconds, the reference will be the abbreviated (lower spatial resolution, higher acceleration) IDEAL IQ obtained in a 10-second breath-hold. In subjects unable to hold their breath, bias determination will not be performed. Precision (test-retest repeatability) for each acquisition method and within each liver segment will be calculated through the coefficient of repeatability [Raunig 2015].	Research visit 1
Quantitative US	Reduce bias introduced by aberration of the US beam introduced by the thick body wall of large BMI subjects. Precision will be quantified in terms of the within-subject coefficient of variation for intra-operator variability, coefficient of reproducibility for inter-operator variability, and intra-class correlation coefficients. Inter- and intra-sonographer agreement will be represented graphically with Bland-Altman plots. The statistical significance of the difference in the body-wall aberration between the two cohorts (healthy weight and obese children) will be assessed using a t-test (for normal data) or Wilcoxon test (non-normal data).	Research visit 1

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Diego Hernando, PhD, University of Wisconsin, Madison; Principal Investigator: Ivan Rosado-Mendez, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2023-1494

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No