Massive Iron Deposit Assessment
Primary Purpose
Iron Overload, Excessive Body Iron Burden
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
R2*-UTE
R2*-GRE
Liver biopsy
Sponsored by
About this trial
This is an interventional diagnostic trial for Iron Overload focused on measuring Sickle cell disease, Thalassemia, Hemochromatosis, Cancer
Eligibility Criteria
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.
Sites / Locations
- St. Jude Children's Research Hospital
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Iron-overloaded
Arm Description
Patients with iron overload or excessive body iron burden, a serious condition resulting from increased dietary gastro¬intestinal absorption, multiple erythrocyte transfusions, or both. Interventions: R2*-UTE, R2*-GRE, and if clinically indicated, liver biopsy.
Outcomes
Primary Outcome Measures
Hepatic Iron Content in the Liver Using Liver Biopsy
Hepatic iron content in the liver using liver biopsy
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01572922
First Posted
April 3, 2012
Last Updated
June 3, 2019
Sponsor
St. Jude Children's Research Hospital
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Regional One Health
1. Study Identification
Unique Protocol Identification Number
NCT01572922
Brief Title
Massive Iron Deposit Assessment
Official Title
Massive Iron Deposit Assessment
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
June 11, 2012 (Actual)
Primary Completion Date
February 28, 2018 (Actual)
Study Completion Date
February 28, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Regional One Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Overload, Excessive Body Iron Burden
Keywords
Sickle cell disease, Thalassemia, Hemochromatosis, Cancer
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
142 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Iron-overloaded
Arm Type
Other
Arm Description
Patients with iron overload or excessive body iron burden, a serious condition resulting from increased dietary gastro¬intestinal absorption, multiple erythrocyte transfusions, or both.
Interventions: R2*-UTE, R2*-GRE, and if clinically indicated, liver biopsy.
Intervention Type
Device
Intervention Name(s)
R2*-UTE
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
R2*-GRE
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Liver biopsy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Hepatic Iron Content in the Liver Using Liver Biopsy
Description
Hepatic iron content in the liver using liver biopsy
Time Frame
up to 30 days after MRI
Title
MRI-derived R2* Values Using 1.5T UTE Technique
Description
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
Secondary Outcome Measure Information:
Title
MRI-derived R2* Using 1.5T GRE Technique
Description
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
Title
MRI Derived R2* Using 1.5T UTE Technique
Description
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
Title
R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements
Description
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
Title
Serum Iron Measurements Compared With 1.5T R2* UTE
Description
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
Title
Transferrin Saturation Measurements
Description
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
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Hankins, MD, MS
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude
Learn more about this trial
Massive Iron Deposit Assessment
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