Massive Iron Deposit Assessment

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01572922
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Regional One Health (Other)
• Enrollment: 142
• Location: 1
• Arm: 1
• Actual Duration (Months): 68.6
• Patients Per Site Per Month: 2.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Iron Overload; Excessive Body Iron Burden	Device: R2*-UTE; Device: R2*-GRE; Procedure: Liver biopsy	N/A

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

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Massive Iron Deposit Assessment
• Actual Study Start Date: Jun 11, 2012
• Actual Primary Completion Date: Feb 28, 2018
• Actual Study Completion Date: Feb 28, 2018

Arms and Interventions

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.

Device: R2*-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.; Device: R2*-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.; Procedure: Liver 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.

Outcome Measures

Primary Outcome Measures

1. Hepatic Iron Content in the Liver Using Liver Biopsy [up to 30 days after MRI]

   Hepatic iron content in the liver using liver biopsy

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Regional One Health

Investigators

• Principal Investigator: Jane Hankins, MD, MS, St. Jude Children's Research Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 11, 2016

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT01572922
• Other Study ID Numbers: MIDAS; R01DK088988
• First Posted: Apr 6, 2012
• Last Update Posted: Jun 11, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by St. Jude Children's Research Hospital: Sickle cell disease; Thalassemia; Hemochromatosis; Cancer
• Additional relevant MeSH terms: Iron Overload

Study Results

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 Detail	One arm study

Arm/Group Title	Arm 1
Arm/Group Description	All eligible patients with history of 12 or more lifetime erythrocyte transfusions, and need for liver iron content assessment.
Period Title: Overall Study
STARTED	142
COMPLETED	139
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Arm 1
Arm/Group Description	All eligible patients with history of 12 or more lifetime erythrocyte transfusions, and need for liver iron content assessment
Overall Participants	142
Age (Count of Participants)
<=18 years	85 59.9%
Between 18 and 65 years	57 40.1%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	15.9
Sex: Female, Male (Count of Participants)
Female	79 55.6%
Male	63 44.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 5.6%
Not Hispanic or Latino	131 92.3%
Unknown or Not Reported	3 2.1%
Race/Ethnicity, Customized (Count of Participants)
Asian	10 7%
Black or African American	85 59.9%
White	40 28.2%
More than one race	1 0.7%
Unknown or Not Reported	6 4.2%
Region of Enrollment (Count of Participants)
United States	142 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2*-UTE measurement.

Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2*-UTE measurement
Measure Participants	41
Median (Full Range) [mcg]	19.8

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2*-UTE measurement.

Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2*-UTE measurement.
Measure Participants	41
Median (Full Range) [Hz]	864.4

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Iron-overloaded patients had 1.5T R2*-GRE measurements.

Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Iron-overloaded patients defined as having more than 12 transfusions in their lifetime as measured with R2* using 1.5T GRE.
Measure Participants	139
Median (Full Range) [Hz]	333.8

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Iron-overloaded patients had 1.5T R2*-UTE-measurement.

Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Iron-overloaded patients with R2* using 1.5T UTE
Measure Participants	139
Median (Full Range) [HZ]	319.2

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

1.5T R2*-UTE from eligible patients who had 1.5T R2*-UTE, serum iron, and transferrin saturation measurements.

Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Iron-overloaded patients with R2* using 1.5T UTE
Measure Participants	104
Median (Full Range) [Hz]	340.8

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Iron-overloaded patients had 1.5T R2*-UTE and serum iron and transferrin saturation measurements.

Arm/Group Title	Serum Iron Measurements
Arm/Group Description	Serum iron measurements from eligible patients had 1.5T R2*-UTE and serum iron and transferrin saturation measurements.
Measure Participants	104
Median (Full Range) [ug/dL]	156.5

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Iron-overloaded patients had 1.5T R2*-UTE and serum iron and transferrin saturation measurements.

Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Iron-overloaded patients with 1.5T R2*-UTE and serum iron and transferrin saturation measurements.
Measure Participants	104
Median (Full Range) [percentage]	71

Adverse Events

Time Frame	Time frame for adverse event reporting is 10 days following the last study procedure for eligible patients.
Arm/Group Title	Iron-overloaded Patients
Arm/Group Description	Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2*-UTE measurement
All Cause Mortality
	Iron-overloaded Patients
	Affected / at Risk (%)	# Events
Total	1/142 (0.7%)
Serious Adverse Events
	Iron-overloaded Patients
	Affected / at Risk (%)	# Events
Total	1/142 (0.7%)
Gastrointestinal disorders
Infections and infestations	1/142 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Iron-overloaded Patients
	Affected / at Risk (%)	# Events
Total	2/142 (1.4%)
Gastrointestinal disorders
abdominal pain	1/142 (0.7%)	1
Psychiatric disorders
Anxiety	1/142 (0.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.