Iron OverloadNCT01572922
Massive Iron Deposit Assessment
A study testing R2*-UTE, R2*-GRE and Liver biopsy in people with Iron Overload and Excessive Body Iron Burden, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Iron Overload, Excessive Body Iron Burden
- What is being tested?
- R2*-UTE, R2*-GRE and Liver biopsy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jun 2012to 28 Feb 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- History of 12 or more lifetime erythrocyte transfusions, AND
- Need for liver iron content assessment (by MRI or liver biopsy)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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.
Read the 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.
- Conditions
- Iron Overload, Excessive Body Iron Burden
- Being tested
- R2*-UTE, R2*-GRE, Liver biopsy
- Keywords
- Sickle cell disease, Thalassemia, Hemochromatosis, Cancer
- Medical subject headings
- Iron Overload, Anemia, Sickle Cell, Thalassemia, Hemochromatosis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R2*-UTEDevice
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.
R2*-GREDevice
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.
Liver biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Iron-overloaded | Other | 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. Receives: Device: R2*-UTE; Device: R2*-GRE; Procedure: Liver biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic Iron Content in the Liver Using Liver Biopsy
Hepatic iron content in the liver using liver biopsy
Measured: up to 30 days after MRI
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.
Measured: Up to 30 days after MRI
Secondary outcomes (5)
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.
Measured: Up to 30 days after MRI
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.
Measured: up to 30 days after MRI
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.
Measured: Up to 30 days after MRI
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.
Measured: Up to 30 days after MRI
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.
Measured: Up to 30 days after MRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2012 (estimated)
- Study start11 Jun 2012
- Primary completion28 Feb 2018
- Study completion28 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Iron OverloadStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Regional One Health
- Responsible party
- Sponsor
- Investigators
- Jane Hankins, MD, MS, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01572922
- Sponsor's protocol ID
- MIDAS
- Other IDs
- R01DK088988
- Status last verified
- Apr 2019
- First submitted
- 3 Apr 2012
- Last updated
- 11 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Massive Iron Deposit Assessment
- ClinicalTrials.gov ID
- NCT01572922
- Acronym / sponsor ID
- MIDAS
- Conditions
- Iron Overload, Excessive Body Iron Burden
- Keywords
- Sickle cell disease, Thalassemia, Hemochromatosis, Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Regional One Health
- Study start
- 11 Jun 2012 (actual)
- Primary completion
- 28 Feb 2018 (actual)
- Study completion
- 28 Feb 2018 (actual)
- First posted
- 6 Apr 2012 (estimated)
- Results
- Posted 21 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Iron-overloaded | Other | Device: R2*-UTE, Device: R2*-GRE, Procedure: Liver biopsyPatients 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- History of 12 or more lifetime erythrocyte transfusions, AND
- Need for liver iron content assessment (by MRI or liver biopsy)
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| R2*-UTEUltra 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. | Device | Iron-overloaded |
| R2*-GREGradient-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. | Device | Iron-overloaded |
| Liver biopsyIndications 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. | Procedure or surgery | Iron-overloaded |
Primary outcome
Hepatic Iron Content in the Liver Using Liver Biopsy
Time frame: up to 30 days after MRI
Hepatic iron content in the liver using liver biopsy
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.
5 secondary outcomes
MRI-derived R2* Using 1.5T GRE Technique
Time frame: Up to 30 days after MRI
MRI Derived R2* Using 1.5T UTE Technique
Time frame: 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
Serum Iron Measurements Compared With 1.5T R2* UTE
Time frame: Up to 30 days after MRI
Transferrin Saturation Measurements
Time frame: Up to 30 days after MRI
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane Hankins, MD, MS principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing R2*-UTE, R2*-GRE and Liver biopsy in people with Iron Overload and Excessive Body Iron Burden, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic Iron Content in the Liver Using Liver Biopsy (time frame: up to 30 days after MRI). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2019.