Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content

Confounder-Corrected Quantitative Magnetic Resonance Imaging (MRI) Biomarker of Hepatic Iron Content

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Iron Overload; Hemosiderosis; Hemochromatosis
• Intervention / Treatment: Device: MRI

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 Type: Observational
• Enrollment (Estimated): 220

Contacts and Locations

• Study Contact: Name: Scott Reeder, MD, PhD; Phone Number: 608-265-9964; Email: sreeder@uwhealth.org
• Study Contact Backup: Name: Diego Hernando, PhD; Phone Number: 608-265-7590; Email: dhernando@uwhealth.org

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94087
      • Stanford University
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas-Southwestern
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • University of Wisconsin, Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 89 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants with known or suspected iron overload, plus a control cohort

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient Group; Subjects with known or suspected iron overload will undergo serum ferritin measurement and an MRI scan.	Device: MRI; R2 MRI scan; Other Names: Magnetic Resonance Imaging
Control Group; Subjects with no known history of iron overload or liver disease will undergo an MRI scan.	Device: MRI; R2 MRI scan; Other Names: Magnetic Resonance Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calibration curve of liver R2* vs LIC measured by Ferriscan at each of the sites	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Precision: Difference in UW-measured R2* vs Average	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.	2 years
Diagnostic Accuracy	In addition to correlation with liver iron concentration (technical accuracy), the diagnostic accuracy through receiver operator characteristic curve analysis will also be determined.	2 years
Robustness Assessed via Linear Mixed Effects Regression	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.	2 years

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Johns Hopkins University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Stanford University; University of Texas
• Investigators: Principal Investigator: Scott Reeder, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Hernando D, Zhao R, Yuan Q, Aliyari Ghasabeh M, Ruschke S, Miao X, Karampinos DC, Mao L, Harris DT, Mattison RJ, Jeng MR, Pedrosa I, Kamel IR, Vasanawala S, Yokoo T, Reeder SB. Multicenter Reproducibility of Liver Iron Quantification with 1.5-T and 3.0-T MRI. Radiology. 2023 Feb;306(2):e213256. doi: 10.1148/radiol.213256. Epub 2022 Oct 4.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2015
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: December 12, 2013
• First Submitted That Met QC Criteria: December 27, 2013
• First Posted (Estimated): January 1, 2014

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Iron overload
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Iron Metabolism Disorders; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Iron Overload; Hemochromatosis; Hemosiderosis
• Other Study ID Numbers: 2013-1174; A539300 (Other Identifier: UW Madison); SMPH/RADIOLOGY/RADIOLOGY* (Other Identifier: UW Madison); R01DK100651 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Case report forms will be coded with a unique study identification number and sent to with the coordinating center by courier. Images will be shared shared using secure FTP server.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes