Massive Iron Deposit Assessment

• ClinicalTrials.gov Identifier: NCT01572922
• Recruitment Status: Completed
• First Posted: April 6, 2012
• Results First Posted: May 21, 2019
• Last Update Posted: June 11, 2019
• Sponsor: St. Jude Children's Research Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Regional One Health
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Tracking Information

• First Submitted Date: April 3, 2012
• First Posted Date: April 6, 2012
• Results First Submitted Date: March 1, 2019
• Results First Posted Date: May 21, 2019
• Last Update Posted Date: June 11, 2019
• Actual Study Start Date: June 11, 2012
• Actual Primary Completion Date: February 28, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 3, 2019)

• 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.

Original Primary Outcome Measures (submitted: April 4, 2012)

• Hepatic iron content in the liver using using liver biopsy [ Time Frame: up to 30 days after MRI ]
  The liver biopsies will be obtained as indicated by good clinical management practice, and it is expected that most research participants who will receive the liver biopsy will have an inconclusive result by the R2*-GRE method. The iron quantification assessed in liver biopsies will be correlated with the R2*-UTE signals. If the correlation is sufficiently high, then a statistical model relating HIC by R2*-UTE and liver biopsy values will be established, as was done for R2*-GRE.32
• Hepatic iron content in the liver using the 1.5T R2*-UTE technique [ Time Frame: once, at or near patient enrollment ]

Current Secondary Outcome Measures (submitted: June 3, 2019)

• 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.
• 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.
• 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.
• 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.
• Transferrin Saturation Measurements [ Time Frame: 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Massive Iron Deposit Assessment
• Official Title: Massive Iron Deposit Assessment

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Iron Overload
• Excessive Body Iron Burden

Intervention

• 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.

Study Arms

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.

Interventions:

• Device: R2*-UTE
• Device: R2*-GRE
• Procedure: Liver biopsy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 26, 2019): 142
• Original Estimated Enrollment (submitted: April 4, 2012): 235
• Actual Study Completion Date: February 28, 2018
• Actual Primary Completion Date: February 28, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01572922
• Other Study ID Numbers: MIDAS; R01DK088988 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: St. Jude Children's Research Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Jude Children's Research Hospital
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: St. Jude Children's Research Hospital
• Verification Date: April 2019