- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01572922
Massive Iron Deposit Assessment
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Iron-overloaded
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. |
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.
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.
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hepatic Iron Content in the Liver Using Liver Biopsy
Time Frame: up to 30 days after MRI
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Hepatic iron content in the liver using liver biopsy
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up to 30 days after MRI
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MRI-derived R2* Values Using 1.5T UTE Technique
Time Frame: 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.
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Up to 30 days after MRI
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MRI-derived R2* Using 1.5T GRE Technique
Time Frame: 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.
|
Up to 30 days after MRI
|
MRI Derived R2* Using 1.5T UTE Technique
Time Frame: 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.
|
up to 30 days after MRI
|
R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements
Time Frame: 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.
|
Up to 30 days after MRI
|
Serum Iron Measurements Compared With 1.5T R2* UTE
Time Frame: Up to 30 days after MRI
|
Serum iron measurements from eligible patients had 1.5T R2*-UTE and serum iron and transferrin saturation measurements.
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Up to 30 days after MRI
|
Transferrin Saturation Measurements
Time Frame: Up to 30 days after MRI
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Iron Transferrin Saturation in % measurements Transferrin Saturation measurements from eligible patients had 1.5T R2*-UTE and serum iron and transferrin saturation measurements.
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Up to 30 days after MRI
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MIDAS
- R01DK088988 (NIH)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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