Massive Iron Deposit Assessment

NCT01572922 | Completed Results FDA Device

• 2 other identifiers: MIDASR01DK088988
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 1

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.

Conditions

Iron Overload; Excessive Body Iron Burden

Keywords

Sickle cell disease; Thalassemia; Hemochromatosis; Cancer

Outcome Measures

Primary Outcomes (2)

• Hepatic Iron Content in the Liver Using Liver Biopsy

  Hepatic iron content in the liver using liver biopsy

  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.

  Up to 30 days after MRI

Secondary Outcomes (5)

• MRI-derived R2* Using 1.5T GRE Technique

  Up to 30 days after MRI

• MRI Derived R2* Using 1.5T UTE Technique

  up to 30 days after MRI

• R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements

  Up to 30 days after MRI

• Serum Iron Measurements Compared With 1.5T R2* UTE

  Up to 30 days after MRI

• Transferrin Saturation Measurements

  Up to 30 days after MRI

Study Arms (1)

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.

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

Interventions

R2*-UTE DEVICE

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.

Iron-overloaded

R2*-GRE DEVICE

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.

Iron-overloaded

Liver biopsy PROCEDURE

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.

Iron-overloaded

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

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

MeSH Terms

Conditions

Iron Overload; Anemia, Sickle Cell; Thalassemia; Hemochromatosis; Neoplasms

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors

Results Point of Contact

• Title: Jane Hankins, MD
• Organization: St. Jude Children's Research Hospital

Jane.Hankins@stjude.org

866-278-5833

Study Officials

• Jane Hankins, MD, MS

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2012
• First Posted: April 6, 2012
• Study Start: June 11, 2012
• Primary Completion: February 28, 2018
• Study Completion: February 28, 2018
• Last Updated: June 11, 2019
• Results First Posted: May 21, 2019

Record last verified: 2019-04

Locations

US (1)