Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content

• Conditions: Iron Overload; Hemochromatosis; Hemosiderosis
• Interventions: Device: MRI

• Registration Number: NCT02025543
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

The purpose of this multi-site research is to validate a rapid magnetic resonance based confounder-corrected R-2 mapping method as a quantitative imaging biomarker of liver iron concentrations.

Detailed Description

This multi-center, multi-vendor study will validate a rapid magnetic resonance-based confounder-corrected R2\* mapping method as a quantitative imaging biomarker of liver iron concentration (LIC). Excessive accumulation of iron in various organs, including the liver, which affects both adult and pediatric populations, is toxic and requires treatment aimed at reducing body iron stores. Measurement of LIC is critical for detection and staging of iron overload, and for monitoring iron-reducing chelator therapies that are expensive and have side effects. Magnetic Resonance Imaging (MRI) is a widely available, accessible, and safe technology, and it is very sensitive to the presence of iron in tissue. Translation of an MRI biomarker of liver iron concentration into broad clinical use requires that it is clinically feasible, precise, robust to changes in scan parameters, calibrated to a validated reference standard of LIC, and is reproducible across sites and manufacturers. There are currently no available MRI methods that meet these requirements. R2\*-MRI holds the greatest promise to meet these requirements. R2\* mapping can be performed very rapidly with whole-liver 3D coverage in a single 20s breath-hold.

Protocol Modification approved to include additional liver susceptibility measurements for approximately 10 participants (already enrolled at the UW) via recently acquired Superconducting Quantum Interference Device (SQUID). The completion of this additional imaging will depend upon the successful set up and installation of this device.

Per a protocol amendment approved on 10/11/21, the investigators are re-opening the study and increasing enrollment for control subjects. Up to 20 control subjects (changed from 5) will be enrolled.

Study Timeline

• Study First Submitted: 2013-12-12
• Study First Submitted QC: 2013-12-27
• Study First Posted: 2014-01-01
• Study Start: 2015-08-12
• Status Verified: 2024-09
• Last Update Submitted: 2025-01-16
• Last Update Posted: 2025-01-17
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• know or suspected iron overload
• minimum age: Stanford- 8years , University of Wisconsin - 10 years, John Hopkins follow- 10 years, University of Texas-Southwestern - 18 years

Exclusion Criteria

• contraindication to magnetic resonance imaging

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control Group	MRI	Subjects with no known history of iron overload or liver disease will undergo an MRI scan.
Patient Group	MRI	Subjects with known or suspected iron overload will undergo serum ferritin measurement and an MRI scan.

Primary Outcome Measures

Name	Time	Method
Calibration curve of liver R2* vs LIC measured by Ferriscan at each of the sites	1 year	The hypothesis is that equivalence between R2 measured with different protocols with higher repeatability than standard MRI iron imaging measurement and with linear calibration to liver iron concentration will be demonstrated. This project will be considered a success if the reproducibility of confounder-corrected R2 MRI is established: the hypothesis is that calibrations at all sites will be equivalent.

Secondary Outcome Measures

Name	Time	Method
Diagnostic Accuracy	2 years	In addition to correlation with liver iron concentration (technical accuracy), the diagnostic accuracy through receiver operator characteristic curve analysis will also be determined.
Precision: Difference in UW-measured R2* vs Average	2 years	Repeat scans will be used at each site to determine precision of R2 liver iron concentration. Repeat scans on n=25 subjects per site will be used to determine Bland-Altman 95% limits of agreement (LOA) by plotting the difference in UW-measured R2\* vs average.
Robustness Assessed via Linear Mixed Effects Regression	2 years	At each site and field strength, R2\* measurements from the eight different protocols will be compared to assess robustness. Robustness will be assessed via linear mixed effects regression.

Trial Locations

Locations (4)

Stanford University; 🇺🇸 Palo Alto, California, United States

University of Texas-Southwestern; 🇺🇸 Dallas, Texas, United States

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

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States