Excessive Body Iron Burden, Iron Overload
Conditions
Keywords
Sickle cell disease, Thalassemia, Hemochromatosis, Cancer
Brief summary
Iron overload is a severe complication of multiple blood transfusions. As the body has no physiologic mechanism for clearing iron, repeated transfusions cause iron accumulation in organs and lead to iron toxicity. Accurate assessment of iron overload is paramount to quantify excessive iron accumulation and to monitor response to iron chelation therapy. Magnetic resonance imaging (MRI) methods have been used to noninvasively measure hepatic iron concentration (HIC). Although MRI-based measurements of transverse relaxation rates (R2 and R2\*) accurately predict biopsy-proven HICs below 15 mg Fe/g, previous studies have shown that their precision is limited for HICs above 15 mg Fe/g and inaccurate above 25 mg Fe/g. Current R2\* gradient-echo (GRE) MR techniques fail occasionally for very high iron overloads (HIC \ 15-25 mg Fe/g) and always for massive iron overloads (HIC \> 25 mg Fe/g) because R2\* is so high that the MR signal decays before it can be measured accurately. Overall accrual: 200 patients Purpose: To determine if a new MRI (UTE) can measure the amount of iron in the liver of people with large amounts of iron and compare the results with the same patient's liver bx. Estimated patient accrual is 150. It is estimated that 41 of these patients will have clinical indication for liver biopsy.
Detailed description
The MIDAS study is a prospective and non-therapeutic study that will test a new MRI technique for the assessment of iron overload in the liver: the newly developed ultra short echo time (UTE), R2\*-UTE. The R2\*-UTE technique, developed by St. Jude investigators from the Department of Radiological Sciences, will be first tested in healthy volunteers for feasibility and implementation of the technique. The technique will then be tested in research participants, who will have both the R2\*-GRE and the R2\*-UTE techniques performed, in addition to a liver biopsy for liver iron quantitation if clinically indicated. Quantitation of liver tissue iron will be done at Mayo Clinic Laboratory in Rochester, Minnesota. Primary Objective: * To test the association of hepatic iron content (HIC) measured with the newly developed 1.5T R2\*-UTE technique and HIC quantified by liver biopsy in subjects with iron overload. Secondary Objectives: * To explore the relationship between 1.5T R2\*-UTE and 1.5T R2\*-GRE measurements in subjects with iron overload. * To explore the relationship between 1.5T R2\*-UTE measurements with iron studies (serum iron and transferrin saturation) in subjects with iron.
Interventions
DEVICER2*-UTE
Ultra short echo time (UTE) magnetic resonance imaging (MRI). Study participants will undergo an MRI examination of the liver on a 1.5T MRI and a 3T MRI scanner each. Because liver biopsy metal needle fragments could interfere with the MRI measurements, the MRI exams will always precede liver biopsy. Multi-echo GRE sequences will be used to acquire images with increasing TEs. Images of the liver will be obtained in transversal slice orientation through the center of the liver at the level of the origin of the main portal vein. At equivalent slice locations R2\*-UTE scans will be performed.
DEVICER2*-GRE
Gradient-echo (GRE) magnetic resonance imaging (MRI). Study participants will undergo an MRI examination of the liver on a 1.5T MRI and a 3T MRI scanner each. Because liver biopsy metal needle fragments could interfere with the MRI measurements, the MRI exams will always precede liver biopsy. Multi-echo GRE sequences will be used to acquire images with increasing TEs. Images of the liver will be obtained in transversal slice orientation through the center of the liver at the level of the origin of the main portal vein. At equivalent slice locations R2\*-UTE scans will be performed.
PROCEDURELiver biopsy
Indications for liver biopsy include, but are not limited, to the need to quantify liver tissue iron and the need to obtain histopathological information of the liver tissue. Liver biopsies will only be performed if clinically indicated and will be done only once per patient. The technique to be used is coaxial percutaneous (transcapsular) technique; however, a coaxial transjugular technique may be performed in subjects with increased bleeding diathesis, since it is associated with less hemorrhagic risk. Healthy volunteers will not undergo liver biopsy.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Regional One Health
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* History of 12 or more lifetime erythrocyte transfusions, AND * Need for liver iron content assessment (by MRI or liver biopsy)
Exclusion criteria
* Presence of certain MR-unsafe foreign material in the body, or other conditions that make the research participant ineligible for an MRI scan per St. Jude policies. * Any condition or chronic illness that in the opinion of the PIs makes participation on study ill-advised.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Iron Content in the Liver Using Liver Biopsy | up to 30 days after MRI | Hepatic iron content in the liver using liver biopsy |
| MRI-derived R2* Values Using 1.5T UTE Technique | Up to 30 days after MRI | Hepatic iron content of the liver using MRI-derived 1.5T R2\*-UTE measurement, with results in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements | Up to 30 days after MRI | MRI-derived R2\* value using 1.5T R2\*-UTE in Hz for patients who have had serum iron and transferrin saturation measurements. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver. |
| MRI-derived R2* Using 1.5T GRE Technique | Up to 30 days after MRI | MRI-derived R2\* Using 1.5T GRE Technique in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver. |
| Transferrin Saturation Measurements | Up to 30 days after MRI | Iron Transferrin Saturation in % measurements Transferrin Saturation measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements. |
| Serum Iron Measurements Compared With 1.5T R2* UTE | Up to 30 days after MRI | Serum iron measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements. |
| MRI Derived R2* Using 1.5T UTE Technique | up to 30 days after MRI | MRI-derived R2\* value using 1.5T R2\*-UTE in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver. |
Countries
United States
Participant flow
Recruitment details
Patients within the St. Jude Network (St. Jude Children's Research Hospital, St. Jude Domestic Affiliates, and the adult Hematology and Oncology program at the University of Tennessee Health Sciences Center) who have history of 12 or more lifetime erythrocyte transfusions, and need for liver iron content assessment.
Pre-assignment details
One arm study
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 All eligible patients with history of 12 or more lifetime erythrocyte transfusions, and need for liver iron content assessment | 142 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Categorical <=18 years | 85 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants |
| Age, Continuous | 15.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 131 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 85 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 6 Participants |
| Race/Ethnicity, Customized White | 40 Participants |
| Region of Enrollment United States | 142 Participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 142 |
| other Total, other adverse events | 2 / 142 |
| serious Total, serious adverse events | 1 / 142 |
Outcome results
Primary
Hepatic Iron Content in the Liver Using Liver Biopsy
Hepatic iron content in the liver using liver biopsy
Time frame: up to 30 days after MRI
Population: Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2\*-UTE measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | Hepatic Iron Content in the Liver Using Liver Biopsy | 19.8 mcg |
Primary
MRI-derived R2* Values Using 1.5T UTE Technique
Hepatic iron content of the liver using MRI-derived 1.5T R2\*-UTE measurement, with results in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
Time frame: Up to 30 days after MRI
Population: Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2\*-UTE measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | MRI-derived R2* Values Using 1.5T UTE Technique | 864.4 Hz |
Secondary
MRI-derived R2* Using 1.5T GRE Technique
MRI-derived R2\* Using 1.5T GRE Technique in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
Time frame: Up to 30 days after MRI
Population: Iron-overloaded patients had 1.5T R2\*-GRE measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | MRI-derived R2* Using 1.5T GRE Technique | 333.8 Hz |
Secondary
MRI Derived R2* Using 1.5T UTE Technique
MRI-derived R2\* value using 1.5T R2\*-UTE in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
Time frame: up to 30 days after MRI
Population: Iron-overloaded patients had 1.5T R2\*-UTE-measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | MRI Derived R2* Using 1.5T UTE Technique | 319.2 HZ |
Secondary
R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements
MRI-derived R2\* value using 1.5T R2\*-UTE in Hz for patients who have had serum iron and transferrin saturation measurements. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every picture taken, this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.
Time frame: Up to 30 days after MRI
Population: 1.5T R2\*-UTE from eligible patients who had 1.5T R2\*-UTE, serum iron, and transferrin saturation measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements | 340.8 Hz |
Secondary
Serum Iron Measurements Compared With 1.5T R2* UTE
Serum iron measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.
Time frame: Up to 30 days after MRI
Population: Iron-overloaded patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | Serum Iron Measurements Compared With 1.5T R2* UTE | 156.5 ug/dL |
Secondary
Transferrin Saturation Measurements
Iron Transferrin Saturation in % measurements Transferrin Saturation measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.
Time frame: Up to 30 days after MRI
Population: Iron-overloaded patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iron-overloaded Patients | Transferrin Saturation Measurements | 71 percentage |