GadoliniumNCT03337594
Gadolinium Retention in Human Bone Tissue in Pediatric Patients
An observational study of Gadolinium and MultiHance, run by Donna Roberts at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Gadolinium, MultiHance, Dotarem
- What is being tested?
- Pre-operative MRI with Dotarem, Pre-operative MRI with MultiHance and Surgery
- Type of treatment
- Surgery or procedure
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2017to 31 Aug 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: All subjects, newborn to 18 years, scheduled for a prospective clinically indicated, contrast-enhanced, cardiac MRI will potentially be eligible for inclusion into the study. Potential subjects will be identified via pediatric cardiology, pediatric cardiothoracic surgery, or clinical schedules and consultation with attending physicians according to satisfaction of the inclusion and exclusion criteria listed above.
Who may be able to join
- 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:
- Patients who have undergone a routine contrast-enhanced MRI using MultiHance contrast agent only for clinical purposes.
- Patients who have undergone a routine contrast-enhanced MRI using Dotarem contrast agent only for clinical purposes.
- Patients who have not been exposed to gadolinium-based contrast agent administration
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: Gadolinium Retention in Human Bone Tissue in Pediatric Patients: a Comparison of Dotarem Versus MultiHance MRI Contrast Agents
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.
Read the detailed 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.
- Being tested
- Pre-operative MRI with Dotarem, Pre-operative MRI with MultiHance, Surgery
- Keywords
- Gadolinium, MultiHance, Dotarem, Contrast agents, Magnetic Resonance Imaging, Gadolinium retention, Pediatric, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-operative MRI with DotaremDrug
Also called gadoterate meglumine
Dotarem® (gadoterate meglumine - Guerbet)
Pre-operative MRI with MultiHanceDrug
Also called gadobenate dimeglumine
MultiHance® (gadobenate dimeglumine - Bracco)
SurgeryProcedure or surgery
Cardiac surgery
| Study group | Role | What they receive |
|---|---|---|
| Control | Pediatric patients who have not been exposed to gadolinium-based contrast agent administration and who require cardiac surgery as part of their standard clinical treatment. Receives: Procedure: Surgery | |
| Dotarem | Pediatric patients who have undergone routine contrast-enhanced MRI using only Dotarem contrast agent for clinical purposes and who require cardiac surgery as part of their standard clinical treatment. Receives: Drug: Pre-operative MRI with Dotarem; Procedure: Surgery | |
| MultiHance | Pediatric patients who have undergone routine contrast-enhanced MRI using only MultiHance contrast agent for clinical purposes and who require cardiac surgery as part of their standard clinical treatment. Receives: Drug: Pre-operative MRI with MultiHance; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: July 2017 to October 2022
Secondary outcomes (1)
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.
Measured: July 2017 to October 2022
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2017
- Study start1 Oct 2017
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for GadoliniumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Donna Roberts
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Standards and Technology
- Responsible party
- Sponsor-investigator, Donna Roberts, Medical University of South Carolina
- Investigators
- Donna R Roberts, M.D., Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03337594
- Sponsor's protocol ID
- Pro00048639
- Status last verified
- Jul 2024
- First submitted
- 6 Nov 2017
- Last updated
- 12 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hesselink JR, Press GA. MR contrast enhancement of intracranial lesions with Gd-DTPA. Radiol Clin North Am. 1988 Jul;26(4):873-87.
PubMed 3289078Hesselink 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.
PubMed 3351041Sherry AD, Caravan P, Lenkinski RE. Primer on gadolinium chemistry. J Magn Reson Imaging. 2009 Dec;30(6):1240-8. doi: 10.1002/jmri.21966.
PubMed 19938036Bellin 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.
PubMed 18358659Hasebroock 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.
PubMed 19368492Darrah 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.
PubMed 21305156White 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.
PubMed 16481910Port 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.
PubMed 18344005Morcos 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.
PubMed 18343072
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gadolinium Retention in Human Bone Tissue in Pediatric Patients: a Comparison of Dotarem Versus MultiHance MRI Contrast Agents
- ClinicalTrials.gov ID
- NCT03337594
- Acronym / sponsor ID
- Pro00048639
- Keywords
- Gadolinium, MultiHance, Dotarem, Contrast agents, Magnetic Resonance Imaging, Gadolinium retention, Pediatric, Bone
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Donna RobertsUniversity, hospital or other
- Collaborators
- National Institute of Standards and Technology
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 9 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | – | Procedure: SurgeryPediatric patients who have not been exposed to gadolinium-based contrast agent administration and who require cardiac surgery as part of their standard clinical treatment. |
| Dotarem | – | Drug: Pre-operative MRI with Dotarem, Procedure: SurgeryPediatric patients who have undergone routine contrast-enhanced MRI using only Dotarem contrast agent for clinical purposes and who require cardiac surgery as part of their standard clinical treatment. |
| MultiHance | – | Drug: Pre-operative MRI with MultiHance, Procedure: SurgeryPediatric patients who have undergone routine contrast-enhanced MRI using only MultiHance contrast agent for clinical purposes and who require cardiac surgery as part of their standard clinical treatment. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- All subjects, newborn to 18 years, scheduled for a prospective clinically indicated, contrast-enhanced, cardiac MRI will potentially be eligible for inclusion into the study. Potential subjects will be identified via pediatric cardiology, pediatric cardiothoracic surgery, or clinical schedules and consultation with attending physicians according to satisfaction of the inclusion and exclusion criteria listed above.
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pre-operative MRI with DotaremAlso: gadoterate meglumineDotarem® (gadoterate meglumine - Guerbet) | Drug | Dotarem |
| Pre-operative MRI with MultiHanceAlso: gadobenate dimeglumineMultiHance® (gadobenate dimeglumine - Bracco) | Drug | MultiHance |
| SurgeryCardiac surgery | Procedure or surgery | Control, Dotarem, MultiHance |
Primary outcome
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.
Time frame: July 2017 to October 2022
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.
1 secondary outcome
Asses the number of exposures to contrast agent as a potential confounder.
Time frame: July 2017 to October 2022
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
- Background: PubMed 3289078Hesselink JR, Press GA. MR contrast enhancement of intracranial lesions with Gd-DTPA. Radiol Clin North Am. 1988 Jul;26(4):873-87.
- Background: PubMed 3351041Hesselink 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.
- Background: PubMed 19938036Sherry AD, Caravan P, Lenkinski RE. Primer on gadolinium chemistry. J Magn Reson Imaging. 2009 Dec;30(6):1240-8. doi: 10.1002/jmri.21966.
- Background: PubMed 18358659Bellin 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.
- Background: PubMed 19368492Hasebroock 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.
- Background: PubMed 21305156Darrah 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.
- Background: PubMed 16481910White 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.
- Background: PubMed 18344005Port 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.
- Background: PubMed 18343072Morcos 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.
- Link to contact Dr. RobertsLink provided by the sponsor.
- NIST: National Institute of Standards and TechnologyLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donna R Roberts, M.D. principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gadolinium and MultiHance, run by Donna Roberts at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: July 2017 to October 2022). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03337594, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2024.