Massive Iron Deposit Assessment

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01572922
First received: April 3, 2012
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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: 235 (200 patients, 35 healthy volunteers)

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 200. It is estimated that 41 of these patients will have clinical indication for liver biopsy.

Volunteer purpose: To test the UTE MRI to ensure it runs correctly before testing in patients, collect data of normal values of iron in the liver in people without iron overload using the UTE MRI and to compare the current MRI (GRE) with the UTE. The UTE MRI will give an accurate value of liver iron in patients with large iron deposits in the liver, therefore providing an accurate means to diagnose, monitor, and provide treatments for participants. This new technology will impact the care of many different populations with iron overload, such as patients with sickle cell disease and thalassemia. Estimated accrual for healthy volunteers is 35.


Condition Intervention
Iron Overload
Excessive Body Iron Burden
Device: R2*-UTE
Device: R2*-GRE
Procedure: Liver biopsy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Massive Iron Deposit Assessment

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Hepatic iron content in the liver using liver biopsy [ Time Frame: up to 30 days after MRI ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1.5T R2*-UTE and 1.5T R2*-GRE measurements [ Time Frame: once, at or near patient enrollment ] [ Designated as safety issue: No ]
    To explore the relationship between 1.5T R2*-UTE and 1.5T R2*-GRE measurements in healthy volunteers and in subjects with iron overload.

  • 1.5T R2*-UTE and serum iron and transferrin saturation measurements [ Time Frame: up to 30 days after MRI ] [ Designated as safety issue: No ]
    To explore the relationship between 1.5T R2*-UTE measurements with iron studies (serum iron and transferrin saturation) in subjects with iron overload


Estimated Enrollment: 235
Study Start Date: April 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Healthy volunteers

Healthy volunteers without iron overload.

Interventions: R2*-UTE, R2*-GRE

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.

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. Healthy volunteers will not have a liver biopsy performed but only the two types of R2*-MRI techniques will be performed and compared.

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 healthy volunteers and 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 overload.
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria - Patients:

  • History of 12 or more lifetime erythrocyte transfusions, AND
  • Need for liver iron content assessment (by MRI or liver biopsy)

Inclusion Criteria - Healthy Volunteers:

  • Age 18 years or older, AND
  • Willingness to undergo MRI testing for investigation and implementation of the R2*-UTE technique.

Exclusion Criteria - Patients:

  • 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.

Exclusion Criteria - Healthy Volunteers:

  • History of blood transfusions in the lifetime.
  • Known history of hereditary hemochromatosis
  • Presence of certain foreign, MR-unsafe material in the body, or other conditions that make the volunteer 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01572922

Contacts
Contact: Jane Hankins, MD, MS 866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Jane Hankins, MD, MS    866-278-5833    info@stjude.org   
Principal Investigator: Jane Hankins, MD, MS         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Jane Hankins, MD, MS St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01572922     History of Changes
Other Study ID Numbers: MIDAS, R01DK088988
Study First Received: April 3, 2012
Last Updated: July 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Sickle cell disease
Thalassemia
Hemochromatosis
Cancer

Additional relevant MeSH terms:
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Iron
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014