Clinical trial NCT02025543: Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content
Official title: Confounder-Corrected Quantitative Magnetic Resonance Imaging (MRI) Biomarker of Hepatic Iron Content
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Iron Overload
Hemochromatosis
Hemosiderosis
Keywords: MRI
Iron overload
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: Stanford University
name: University of Texas
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-01-01
Enrollment: 220
Sex: ALL
Minimum age (years): 8
Maximum age (years): 89
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with known or suspected iron overload, plus a control cohort

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.

Eligibility criteria: 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

Primary outcomes:
measure: Calibration curve of liver R2* vs LIC measured by Ferriscan at each of the sites
timeFrame: 1 year
Secondary outcomes:
measure: Precision: Difference in UW-measured R2* vs Average
timeFrame: 2 years
measure: Diagnostic Accuracy
timeFrame: 2 years
measure: Robustness Assessed via Linear Mixed Effects Regression
timeFrame: 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Dallas
country: United States
facility: University of Texas-Southwestern
state: Texas
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Scott Reeder
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.