Iron OverloadNCT02025543
Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content
An observational study of Iron Overload and Hemochromatosis, run by University of Wisconsin, Madison at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 8 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Iron Overload, Hemochromatosis, Hemosiderosis
- What is being tested?
- MRI
- Type of treatment
- Medical device
- How many people
- 207 participants
- Where
- 4 sitesUnited States
- Study dates
- 12 Aug 2015to Sep 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 89 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Participants with known or suspected iron overload, plus a control cohort
Who may be able to join
- 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
Who cannot join
- contraindication to magnetic resonance imaging
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins University
Baltimore, Maryland, 21218
University of Texas-Southwestern
Dallas, Texas, 75390
University of Wisconsin, Madison
Madison, Wisconsin, 53704
Stanford University
Palo Alto, California, 94087
About this study
Official title: 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.
Read the 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.
- Conditions
- Iron Overload, Hemochromatosis, Hemosiderosis
- Being tested
- MRI
- Keywords
- MRI, Iron overload
- Medical subject headings
- Iron Overload, Hemochromatosis, Hemosiderosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDevice
Also called Magnetic Resonance Imaging
R2 MRI scan
| Study group | Role | What they receive |
|---|---|---|
| Patient Group | Subjects with known or suspected iron overload will undergo serum ferritin measurement and an MRI scan. Receives: Device: MRI | |
| Control Group | Subjects with no known history of iron overload or liver disease will undergo an MRI scan. Receives: Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2014 (estimated)
- Study start12 Aug 2015
- Primary completionSep 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Iron OverloadStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, Stanford University, University of Texas, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Scott Reeder, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02025543
- Sponsor's protocol ID
- 2013-1174
- Other IDs
- A539300, SMPH/RADIOLOGY/RADIOLOGY*, R01DK100651, Protocol Version 12/12/22
- Status last verified
- Aug 2025
- First submitted
- 12 Dec 2013
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
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.
PubMed 36194113Buelo CJ, Velikina J, Mao L, Zhao R, Yuan Q, Ghasabeh MA, Ruschke S, Karampinos DC, Harris DT, Mattison RJ, Jeng MR, Pedrosa I, Kamel IR, Vasanawala S, Yokoo T, Reeder SB, Hernando D. Multicenter, multivendor validation of liver quantitative susceptibility mapping in patients with iron overload at 1.5 T and 3 T. Magn Reson Med. 2025 Jan;93(1):330-340. doi: 10.1002/mrm.30251. Epub 2024 Sep 5.
PubMed 39238238
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Confounder-Corrected Quantitative Magnetic Resonance Imaging (MRI) Biomarker of Hepatic Iron Content
- ClinicalTrials.gov ID
- NCT02025543
- Acronym / sponsor ID
- 2013-1174
- Conditions
- Iron Overload, Hemochromatosis, Hemosiderosis
- Keywords
- MRI, Iron overload
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Johns Hopkins University, Stanford University, University of Texas, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 12 Aug 2015 (actual)
- Primary completion
- Sep 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 1 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient Group | – | Device: MRISubjects with known or suspected iron overload will undergo serum ferritin measurement and an MRI scan. |
| Control Group | – | Device: MRISubjects with no known history of iron overload or liver disease will undergo an MRI scan. |
Who may qualify
- Ages
- 8 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants with known or suspected iron overload, plus a control cohort
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (1 listed)
- contraindication to magnetic resonance imaging
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIAlso: Magnetic Resonance ImagingR2 MRI scan | Device | Control Group, Patient Group |
Primary outcome
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.
3 secondary outcomes
Precision: Difference in UW-measured R2* vs Average
Time frame: 2 years
Diagnostic Accuracy
Time frame: 2 years
Robustness Assessed via Linear Mixed Effects Regression
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Results publication: PubMed 36194113Hernando 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.
- Derived from this study: PubMed 39238238Buelo CJ, Velikina J, Mao L, Zhao R, Yuan Q, Ghasabeh MA, Ruschke S, Karampinos DC, Harris DT, Mattison RJ, Jeng MR, Pedrosa I, Kamel IR, Vasanawala S, Yokoo T, Reeder SB, Hernando D. Multicenter, multivendor validation of liver quantitative susceptibility mapping in patients with iron overload at 1.5 T and 3 T. Magn Reson Med. 2025 Jan;93(1):330-340. doi: 10.1002/mrm.30251. Epub 2024 Sep 5.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Reeder principal investigator
University of Wisconsin, Madison
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Iron Overload and Hemochromatosis, run by University of Wisconsin, Madison at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calibration curve of liver R2* vs LIC measured by Ferriscan at each of the sites (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02025543, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.