An Imaging-based Quantitative Biomarker Assay for NAFLD in Children

NAFLD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06354491
• Other study ID #: 2023-1494
• Status: Recruiting
• Start date: April 1, 2024
• Est. completion date: April 1, 2027

Study information

• Verified date: April 2024
• Source: University of Wisconsin, Madison
• Contact: Gemma Gliori, MS
• Phone: 608-262-7269
• Email: ggliori[@]uwhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: April 1, 2027
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• NAFLD
• NASH
• Non-alcoholic Fatty Liver Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Wisconsin, Madison	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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