Technical Validation of MR Biomarkers of Obesity-Associated NAFLD

University of Wisconsin (UW)

Status: Completed

Conditions: Non-alcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease

Treatments: Diagnostic Test: Liver biopsy; Other: Magnetic Resonance Elastography (MRE)

Study type: Observational

Funder types: Other; Industry; NIH

Identifiers

NCT03674528

5UL1TR002373-04 (U.S. NIH Grant/Contract)

SMPH/RADIOLOGY/RADIOLOGY (Other Identifier)

A539300 (Other Identifier)

Protocol Version 3/8/2022 (Other Identifier)

2R01DK088925-06A1 (U.S. NIH Grant/Contract)

2018-0244

Details and patient eligibility

About

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

Full 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.

Enrollment: 152 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

152 participants in 2 patient groups

Control Group

Description:

Subjects with a BMI of 35 or more will be asked to undergo a single MRE imaging session.

Treatment:

Other: Magnetic Resonance Elastography (MRE)

Patient Group

Description:

Adults that are candidates for weight loss surgery will be asked to participate in four study visits that include MRE imaging and 1 - 2 liver biopsy procedures.

Treatment:

Other: Magnetic Resonance Elastography (MRE)

Diagnostic Test: Liver biopsy