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Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content

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ClinicalTrials.gov Identifier: NCT02025543
Recruitment Status : Recruiting
First Posted : January 1, 2014
Last Update Posted : November 8, 2022
Johns Hopkins University
Stanford University
University of Texas
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Iron Overload Hemochromatosis Hemosiderosis 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.

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Study Type : Observational
Estimated Enrollment : 220 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Confounder-Corrected Quantitative Magnetic Resonance Imaging (MRI) Biomarker of Hepatic Iron Content
Actual Study Start Date : August 12, 2015
Estimated Primary Completion Date : March 24, 2023
Estimated Study Completion Date : March 2024

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 Name: 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 Name: Magnetic Resonance Imaging

Primary Outcome Measures :
  1. Calibration curve of liver R2* vs LIC measured by Ferriscan at each of the sites [ Time Frame: 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 :
  1. Precision: Difference in UW-measured R2* vs Average [ Time Frame: 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.

  2. Diagnostic Accuracy [ Time Frame: 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.

  3. Robustness Assessed via Linear Mixed Effects Regression [ Time Frame: 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 89 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants with known or suspected iron overload, plus a control cohort

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02025543

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Contact: Scott Reeder, MD, PhD 608-265-9964 sreeder@uwhealth.org
Contact: Diego Hernando, PhD 608-265-7590 dhernando@uwhealth.org

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United States, California
Stanford University Active, not recruiting
Palo Alto, California, United States, 94087
United States, Maryland
Johns Hopkins University Active, not recruiting
Baltimore, Maryland, United States, 21218
United States, Texas
University of Texas-Southwestern Active, not recruiting
Dallas, Texas, United States, 75390
United States, Wisconsin
University of Wisconsin, Madison Recruiting
Madison, Wisconsin, United States, 53704
Contact: Gemma Gliori, MS    608-262-7269    ggliori@uwhealth.org   
Contact: Suzanne Hanson, BS    608-263-7421    shanson@uwhealth.org   
Principal Investigator: Scott Reeder, MD, PhD         
Sponsors and Collaborators
University of Wisconsin, Madison
Johns Hopkins University
Stanford University
University of Texas
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Scott Reeder University of Wisconsin, Madison
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT02025543    
Other Study ID Numbers: 2013-1174
A539300 ( Other Identifier: UW Madison )
SMPH/RADIOLOGY/RADIOLOGY* ( Other Identifier: UW Madison )
R01DK100651 ( U.S. NIH Grant/Contract )
First Posted: January 1, 2014    Key Record Dates
Last Update Posted: November 8, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by University of Wisconsin, Madison:
Iron overload
Additional relevant MeSH terms:
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Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn