Clinical trial NCT03674528: Technical Validation of MR Biomarkers of Obesity-Associated NAFLD
Official title: Technical Validation of Magnetic Resonance Biomarkers of Obesity-Associated Non-Alcoholic Fatty Liver Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-Alcoholic Fatty Liver Disease
Non-alcoholic Steatohepatitis
Keywords: MRI
MRE
Liver Disease
Liver Fibrosis
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: GE Healthcare
name: Pfizer
name: Siemens Medical Solutions
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2018-09-17
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Phase 1 participants will be healthy adults with a BMI of greater/equal to 35 kilograms per meter squared.

Phase 2 participants must be eligible for weight loss surgery and willing to undergo a liver biopsy procedure.

Brief 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

Detailed 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.

Eligibility 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)

Primary outcomes:
measure: Optimization of MRE for 2 dimensional and 3 dimensional methods
timeFrame: Up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Scott Reeder, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: