An Imaging-based Quantitative Biomarker Assay for NAFLD in Children

Recruiting

• Conditions: NASH; NAFLD
• Interventions: Device: Magnetic Resonance Imaging (MRI); Device: Ultrasound (US)

• Registration Number: NCT06354491
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

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).

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 Timeline

• Study Start: 2024-04-01
• Study First Submitted: 2024-04-03
• Study First Submitted QC: 2024-04-03
• Study First Posted: 2024-04-09
• Status Verified: 2024-08
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-11
• Primary Completion: 2026-04-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Average or low BMI	Magnetic Resonance Imaging (MRI)	Children with BMI under the 85th percentile for age and sex
Average or low BMI	Ultrasound (US)	Children with BMI under the 85th percentile for age and sex
High BMI	Ultrasound (US)	Children with BMI in the 95th percentile or higher for age and sex
High BMI	Magnetic Resonance Imaging (MRI)	Children with BMI in the 95th percentile or higher for age and sex

Primary Outcome Measures

Name	Time	Method
Quantitative US	Research visit 1	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).
MRI	Research visit 1	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 \[Raunig 2015\].

Trial Locations

Locations (1)

University of Wisconsin, Madison; 🇺🇸 Madison, Wisconsin, United States