Quantitative Susceptibility Mapping (QSM) to Guide Iron Chelating Therapy

NCT04171635 | Completed

• 2 other identifiers: 1706018263R01DK116126-01A1
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 2

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\*.

Conditions

MRI Scans

Keywords

Quantitative Susceptibility Mapping; Iron chelating therapy; Iron overload; Liver iron concentration; erythrocyte transfusion; liver transplantation; magnetic resonance imaging; thalassemia major

Outcome Measures

Primary Outcomes (1)

• Demonstration of efficacy of quantitative susceptibility mapping (QSM) MRI in quantifying liver iron concentration (LIC)

  Investigators will assess the accuracy of liver iron concentrations measured by QSM in patients before liver transplant with histologic examination using the gold standard chemical measurement of LIC in liver explants.

  Five years

Secondary Outcomes (12)

• Fibrosis as determined by in vivo R2*, an MRI method that provides quantitative information on iron levels

  Five years

• Fibrosis as determined by in vitro R2*, an MRI method that provides quantitative information on iron levels

  Five years

• Fibrosis as determined by in vivo hQSM, an MRI post-processing technique that provides quantitative information on iron levels

  Five years

• Fibrosis as determined by in vitro hQSM, an MRI post processing technique that provides quantitative information on iron levels

  Five years

• Steatosis as determined by in vivo R2*, an MRI method that provides quantitative information on iron levels

  Five years

Study Arms (2)

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).

Radiation: Quantitative Susceptibility Mapping (QSM) Magnetic Resonance Imaging (MRI); Radiation: R2* Magnetic Resonance Imaging (MRI)

Healthy subjects

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

Radiation: Quantitative Susceptibility Mapping (QSM) Magnetic Resonance Imaging (MRI); Radiation: R2* Magnetic Resonance Imaging (MRI)

Interventions

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

Healthy subjects; Patients with transfusional iron overload

R2* Magnetic Resonance Imaging (MRI) RADIATION

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

Healthy subjects; Patients with transfusional iron overload

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy subjects will be selected from the community through personal contact and written description of the research, and online advertising. Subjects will be selected at Columbia from those awaiting liver transplant to be enrolled in the study.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Columbia University: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Liver explants to be obtained from the Department of Pathology and Cell Biology at Columbia after all clinical pathological examinations have been completed and the specimens would otherwise be discarded. Specimens are initially stored with identifying information but will be de-identified by the Study Pathologist prior to transport to Weill Cornell Medicine.

MeSH Terms

Conditions

Iron Overload; beta-Thalassemia

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Gary M Brittenham, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Yi Wang, PhD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Sujit S Sheth, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 21, 2019
• Study Start: December 16, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)