Gadolinium Retention in Human Bone Tissue in Pediatric Patients

Magnetic Resonance Imaging Clinical Trial

Official title:

Gadolinium Retention in Human Bone Tissue in Pediatric Patients: A Comparison of Dotarem Versus MultiHance MRI Contrast Agents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03337594
• Other study ID #: Pro00048639
• Status: Recruiting
• Start date: October 1, 2017
• Est. completion date: July 2024

Study information

• Verified date: May 2024
• Source: Medical University of South Carolina
• Contact: Sam Bidwell
• Phone: (843)792-1930
• Email: bidwells[@]musc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to compare contrast agents, Dotarem or MultiHance. The study will test to see how much of these two contrast agents are deposited in the bones or tissues of pediatric patients. The patients receiving contrast will then be compared against pediatric patients who have not received any contrast prior to cardiac surgeries.

Description:

When injected into the body, gadolinium contrast medium makes certain tissues, abnormalities or disease processes more clearly visible on a magnetic resonance imaging (MRI) scans and therefore gadolinium based contrast agents (GBCAs) are widely used in medical imaging. Recently, new evidence suggests that following GBCA administration, gadolinium can be deposited in body tissues even in the presence of normal renal function. Therefore, it is essential to ensure that significant accumulation of free Gd3+ is not occurring in the bones of children undergoing clinical contrasted MRI scans. This is particularly important for those pediatric patients who will undergo multiple repeated MRI exams throughout their lifetime and thereby be exposed to a large cumulative dose of gadolinium contrast. As the differences in stability between the various GBCAs may be a factor in gadolinium exposure, the primary objective of this study is to assess gadolinium deposition in the bones of pediatric patients in two patient groups: 1. patients who received IV administration of gadolinium contrast agent (Dotarem) and 2. patients who received IV administration of gadolinium contrast agent (MultiHance).

Once acquired the samples will be analyzed at an off-site facility, National Institute of Standards and Technology (NIST), using standardized equipment which has been certified for measuring gadolinium concentration in contrast agent samples. A signed agreement for the transfer of non-proprietary biological material between MUSC and NIST covers the transfer of the samples.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Female or male pediatric patient (patients aged newborn to 18 years old at the time of the MRI scan).

• Patients who require cardiac surgery for clinical purposes and meet one of the following three criteria:

1. Patients who have undergone a routine contrast-enhanced MRI using MultiHance contrast agent only for clinical purposes.

2. Patients who have undergone a routine contrast-enhanced MRI using Dotarem contrast agent only for clinical purposes.

3. Patients who have not been exposed to gadolinium-based contrast agent administration

Exclusion Criteria:

• Patient with abnormal renal function (defined as eGFR MDRD<30 ml/min/1.73m2).

• Patient previously exposed to any other type of MRI gadolinium based contrast agent either at MUSC or at an outside facility

• Pregnant or breast feeding female patient

• Patient with a contraindication to MRI (e.g., pacemaker, aneurysm clip, severe claustrophobia, infusion pumps, cochlear implants metallic or others according to standard practice at MUSC).

Related Conditions & MeSH terms

• Dotarem
• Gadolinium
• Gadolinium Retention
• Magnetic Resonance Imaging
• MultiHance

Intervention

Drug:
• Pre-operative MRI with Dotarem
Dotarem® (gadoterate meglumine - Guerbet)
• Pre-operative MRI with MultiHance
MultiHance® (gadobenate dimeglumine - Bracco)

Procedure:
• Surgery
Cardiac surgery

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Donna Roberts	National Institute of Standards and Technology

Country where clinical trial is conducted

United States, 

References & Publications (9)

Bellin MF, Van Der Molen AJ. Extracellular gadolinium-based contrast media: an overview. Eur J Radiol. 2008 May;66(2):160-7. doi: 10.1016/j.ejrad.2008.01.023. Epub 2008 Mar 20. — View Citation

Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, Hannigan RE. Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics. 2009 Nov;1(6):479-88. doi: 10.1039/b905145g. Epub 2009 Sep 16. — View Citation

Hasebroock KM, Serkova NJ. Toxicity of MRI and CT contrast agents. Expert Opin Drug Metab Toxicol. 2009 Apr;5(4):403-16. doi: 10.1517/17425250902873796. — View Citation

Hesselink JR, Healy ME, Press GA, Brahme FJ. Benefits of Gd-DTPA for MR imaging of intracranial abnormalities. J Comput Assist Tomogr. 1988 Mar-Apr;12(2):266-74. doi: 10.1097/00004728-198803000-00015. — View Citation

Hesselink JR, Press GA. MR contrast enhancement of intracranial lesions with Gd-DTPA. Radiol Clin North Am. 1988 Jul;26(4):873-87. — View Citation

Morcos SK. Extracellular gadolinium contrast agents: differences in stability. Eur J Radiol. 2008 May;66(2):175-9. doi: 10.1016/j.ejrad.2008.01.025. Epub 2008 Mar 14. — View Citation

Port M, Idee JM, Medina C, Robic C, Sabatou M, Corot C. Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review. Biometals. 2008 Aug;21(4):469-90. doi: 10.1007/s10534-008-9135-x. Epub 2008 Mar 15. — View Citation

Sherry AD, Caravan P, Lenkinski RE. Primer on gadolinium chemistry. J Magn Reson Imaging. 2009 Dec;30(6):1240-8. doi: 10.1002/jmri.21966. — View Citation

White GW, Gibby WA, Tweedle MF. Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol. 2006 Mar;41(3):272-8. doi: 10.1097/01.rli.0000186569.32408.95. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the gadolinium concentration present in bone tissue in pediatric patients following a standard of care MRI with MultiHance, Dotarem, or without any exposure to contrast.	To determine the gadolinium concentration present in sternum and rib bone tissue in 2 groups of pediatric patients requiring cardiac surgery as part of their standard clinical treatment: (1) patients who had undergone the administration of a standard clinical dose of a linear GBCA (0.1 mmol/kg IV MultiHance), and (2) patients who had undergone the administration of a standard clinical dose of a macrocyclic GBCA (0.1 mmol/kg IV Dotarem). As a control, gadolinium concentration present in sternum bone tissue will also be determined in patients who had not been exposed to GBCA administration prior to surgery.	July 2017 to October 2022
Secondary	Asses the number of exposures to contrast agent as a potential confounder.	Number of exposures to contrast agent is a potential confounder. Thus we will perform linear regression, with concentration as the outcome, and both type of contrast agent (i.e. group) and number of doses as independent variables. Although the sample size is small, we may consider evaluating an interaction between type of contrast and number of doses as an exploratory analysis.	July 2017 to October 2022

External Links

•   Link to contact Dr. Roberts
•   NIST: National Institute of Standards and Technology