Quantitative Susceptibility Mapping (QSM) to Guide Iron Chelating Therapy

NCT ID: NCT04171635

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 42 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-12-16
• Study Completion Date: 2025-12-31

Brief Summary

The overall goal of this research is to help develop a new magnetic resonance (MR) method, Quantitative Susceptibility Mapping (QSM), to improve the measurement of liver iron concentrations without the need for a liver biopsy. Measurement of liver iron is important to diagnose and treat patients who have too much iron in their bodies (iron overload). Liver iron measurements by current MRI methods (R2 and R2*) can be inaccurate because of the effects of fat, fibrosis and other abnormalities. QSM should not be affected by these factors and should be free of these errors. In this study, MRI measurements (QSM, R2 and R2*) of iron in patients before liver transplant will be compared with chemical analysis of iron in liver explants (livers removed from patients undergoing liver transplant). The liver explants would otherwise be discarded. Investigators expect that this study will show that the new MRI method, QSM, is superior to the current MRI methods, R2 and R2*.

Detailed Description

The overall objective of this research is to improve the safety of iron-chelating therapy (ICT) in patients with transfusional iron overload by developing an accurate non-invasive measurement of the liver iron concentration (LIC), the best measure of the body iron burden in all forms of systemic iron overload. The scientific premise is that quantitative susceptibility mapping (QSM) provides a quantitative biophysical connection to LIC. Safe ICT requires careful adjustment of the iron chelator dose to the body iron burden to optimize iron excretion while avoiding chelator toxicity, including gastrointestinal disorders, audiovisual impairment, neutropenia, arthropathy, growth retardation, and hepatic and renal failure. QSM enables accurate measurement of LIC by overcoming the inherent cellular interference in current R2 (=1/T2) and R2* (=R2+R2') estimates that lack a well-defined biophysical connection to the LIC. A fundamental biophysical limitation of the R2 and R2* approaches is that intravoxel contents other than iron, including fibrosis, steatosis and necroinflammation, also alter relaxation. In the liver, paramagnetic iron stored in ferritin and hemosiderin is the dominant susceptibility source for QSM. Consequently, magnetic susceptibility measured by QSM has a simple linear relationship with the concentration of iron in the liver and is little affected by fibrosis, steatosis and necroinflammation. The investigator's research plan has 3 specific aims:

Aim 1. Develop hQSM for accurate measurement of LIC without interfering errors. Investigators will optimize data acquisition and processing for free-breathing navigator acquisition with robust fat-water separation.

Aim 2. Validate hQSM using histology and chemical measurement of LIC in liver explants. Investigators will assess the accuracies of LICs measured by hQSM and R2* in patients before liver transplant with histologic examination using the reference standard of chemical measurement of LIC in liver explants.

Aim 3. Evaluate hQSM in patients with transfusional iron overload under ICT. In patients regularly transfused for thalassemia major, investigators will conduct a double-blind clinical study comparing the accuracy of hQSM and R2* in measuring annual changes in LIC, using regression against the year-long amount of iron administered in red blood cell transfusions and the year-long cumulative dose of iron chelator.

Conditions

MRI Scans

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with transfusional iron overload

The subject population of patients with transfusional iron overload awaiting liver transplant has been chosen because of the clinical indication for MRI examination every three months and the availability of liver explants for analysis after transplant. Explants will receive QSM or R2\* MRI to provide a quantitative biophysical connection to liver iron concentration (LIC).

Quantitative Susceptibility Mapping (QSM) Magnetic Resonance Imaging (MRI)

Intervention Type: RADIATION

Investigators will validate hepatic QSM (hQSM) using histological examination and chemical measurement of liver iron concentration (LIC). Patients will undergo clinical MRI in Aim 1. In patients with increased LIC their liver explants will undergo MRI, pathological examination, and chemical determination of the LIC.

R2* Magnetic Resonance Imaging (MRI)

Intervention Type: RADIATION

Investigators will be able to validate hQSM in measuring liver iron concentration (LIC) by comparing it to this traditional MRI technique

Healthy subjects

Healthy control subjects over the age of 21 with no known hematological or liver disease and no contraindications for MRI

Quantitative Susceptibility Mapping (QSM) Magnetic Resonance Imaging (MRI)

Intervention Type: RADIATION

Investigators will validate hepatic QSM (hQSM) using histological examination and chemical measurement of liver iron concentration (LIC). Patients will undergo clinical MRI in Aim 1. In patients with increased LIC their liver explants will undergo MRI, pathological examination, and chemical determination of the LIC.

R2* Magnetic Resonance Imaging (MRI)

Intervention Type: RADIATION

Investigators will be able to validate hQSM in measuring liver iron concentration (LIC) by comparing it to this traditional MRI technique

Interventions

Quantitative Susceptibility Mapping (QSM) Magnetic Resonance Imaging (MRI)

Investigators will validate hepatic QSM (hQSM) using histological examination and chemical measurement of liver iron concentration (LIC). Patients will undergo clinical MRI in Aim 1. In patients with increased LIC their liver explants will undergo MRI, pathological examination, and chemical determination of the LIC.

Intervention Type: RADIATION

R2* Magnetic Resonance Imaging (MRI)

Investigators will be able to validate hQSM in measuring liver iron concentration (LIC) by comparing it to this traditional MRI technique

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Established diagnosis of thalassemia major
• Treatment with deferasirox formulated as Jadenu® as the sole iron chelating therapy (ICT)
• Regular transfusion with records maintained in the Cornell Thalassemia Program
• 2 years of age or older
• Females who are not pregnant

• Men and women aged 21 years or older
• Able and willing to give consent
• No known hematological and liver disease
• No contraindications for MRI

Exclusion Criteria

• A history of auditory or ocular toxicity related to ICT
• A history of poor adherence to prescribed therapy
• An inability to tolerate MRI examinations
• Treatment for mental illness
• Institutionalization or imprisonment

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Columbia University

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary M Brittenham, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Yi Wang, PhD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Sujit S Sheth, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Site Status: RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Gary M Brittenham, MD

Role: CONTACT

gmb31@cumc.columbia.edu

212-305-7005

Facility Contacts

Yi Wang, PhD

Role: primary

yiwang@med.cornell.edu

(212)-962-2631

Other Identifiers

R01DK116126-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1706018263

Identifier Type: -

Identifier Source: org_study_id