Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content

Iron Overload Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02025543
• Other study ID #: 2013-1174
• Secondary ID: A539300SMPH/RADI
• Status: Enrolling by invitation
• Start date: August 12, 2015
• Est. completion date: September 2024

Study information

• Verified date: April 2024
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 220
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemochromatosis
• Hemosiderosis
• Iron Overload

Intervention

Device:
• MRI
R2 MRI scan

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Texas-Southwestern	Dallas	Texas
United States	University of Wisconsin, Madison	Madison	Wisconsin
United States	Stanford University	Palo Alto	California

Sponsors (5)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Stanford University, University of Texas

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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