Technical Validation of MR Biomarkers of Obesity-Associated NAFLD

Non-Alcoholic Fatty Liver Disease Clinical Trial

— NAFLD  

Official title:

Technical Validation of Magnetic Resonance Biomarkers of Obesity-Associated Non-Alcoholic Fatty Liver Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03674528
• Other study ID #: 2018-0244
• Secondary ID: 2R01DK088925-06A
• Status: Active, not recruiting
• Start date: May 4, 2018
• Est. completion date: September 2024

Study information

• Verified date: December 2023
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The overall goal of this collaborative research program is to develop, validate and translate advanced quantitative magnetic resonance (MR) biomarkers of obesity-associated non-alcoholic fatty liver disease (NAFLD). This protocol represents the research plan for two distinct phases. The first phase is an optimization phase. The second phase is designed to complete a rigorous test of conventional and advanced MRE techniques. Complementary anthropometric, laboratory, and MR measures will also be collected to characterize the cohort and identify factors that affect MRE performance

Description:

The long-term objective of this research is to improve the health of the millions of Americans with or at risk for NAFLD, the most common chronic liver disease and most rapidly growing indication for liver transplantation in the United States. To achieve this objective, an advanced MR-based imaging method will be used to measure liver "stiffness" which is an early sign of disease. This technique has been previously developed and validated and ready to be used for further research. This current protocol will extend previous work by optimizing and validating advanced 2 dimensional and 3 dimensional-magnetic resonance elastography (MRE) methods as non-invasive biomarkers of hepatic inflammation and fibrosis in obese patients at risk for non-alcoholic steatohepatitis (NASH), the histologically more aggressive subset of NAFLD.

Per Amendment approved 4/8/22: MRE exams will be conducted using a PDFF Pocket Phantom purchased by the UCSD from Calimetrix. This phantom consists of vials with known fat fraction which are captured when taking images of the liver. The known fat fractions provide an independent reference and are used for quality assurance purposes.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 152
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (Phase 1 and 2 participants)

• Age of at least 18 years

• Severely obese (BMI = 35 kg/m2) patient

Inclusion Criteria (Phase 2 participants only)

• Cleared for weight-loss surgery

• Willing and able to complete all safety and follow-up procedures

• Willing to allow for the banking of biological samples

Exclusion Criteria (Phase 1 and 2 participants)

• Contraindications to MRI

• Girth or weight that exceeds scanner capacity

• Women of childbearing potential that are pregnant or will be attempting to become pregnant during the study duration.

Exclusion Criteria (Phase 2 participants only)

• Known liver malignancies

• Regular & excessive alcohol consumption within 2 years prior to recruitment

• Use of steatogenic or hepatotoxic drugs

• Clinical or laboratory evidence of liver disease other than Nonalcoholic fatty liver disease (NAFLD)/ Nonalcoholic steatohepatitis (NASH) (e.g. HCV Ab, HBV Ab, ceruloplasmin)

• The subject has increased bleeding risk (i.e., decreased platelets, von Willebrand disease)

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis

Intervention

Other:
• Magnetic Resonance Elastography (MRE)
The MRE scan will several breath holds and will take approximately 30 minutes to complete.

Diagnostic Test:
• Liver biopsy
Subjects undergoing WLS will be asked to allow for liver biopsy samples to be collected during their surgical procedure. The collection of these samples will take approximately 5 minutes to complete.

Locations

Country	Name	City	State
United States	University of California, San Diego	La Jolla	California
United States	University of Wisconsin, Madison	Madison	Wisconsin

Sponsors (6)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	GE Healthcare, National Center for Advancing Translational Sciences (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Pfizer, Siemens Medical Solutions

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Optimization of MRE for 2 dimensional and 3 dimensional methods	Optimize MRE wave-field generation in this subject population to maximize the area of invertible shear waves in the liver into interpretable shear stiffness maps.	Up to 24 months