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Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years
NCT04373564 · Guerbet
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
Official title
Prospective Evaluation of Potential Effects of Repeated Gadolinium-based Contrast Agent (GBCA) Administrations of the Same GBCA on Motor and Cognitive Functions in Neurologically Normal Adults in Comparison to a Non-GBCA Exposed Control Group
About this study
The primary objective of the study is to assess the potential effect of repeated exposure to either a linear or a macrocyclic gadolinium-based contrast agent (GBCA) on change from baseline to Year 5 in composite measure of motor and cognitive function among neurologically normal adults in comparison to a matched non-GBCA- exposed control group.
The secondary objectives comprise the assessment of the following endpoints in GBCA-exposed participants as compared to controls a) changes from baseline in composite measure of motor and cognitive function post-baseline on yearly basis (Years 1 to 4); b) changes from baseline in each individual test of motor and cognitive function on yearly basis (Years 1 to 5). Total Gd concentrations in blood and urine samples on yearly basis (Years 1 to 5) and adverse events will be collected as secondary objectives.
Of note : The study is considered interventional because of the addition of UE-MRI scans for all participants, as well as blood sampling and the administration of the motor and cognitive tests. The GBCA administered as part of the contrast-enhanced MR imaging in the experimental arms is not the intervention in this study. Neither the protocol nor the investigators assign patients to a specific GBCA as part of the study, making this part of the study observational rather than interventional. The participants were already scheduled, prior to study screening, to undergo CE-MRI as part of their clinical care. The choice of GBCA for the CE-MRI will be based on medical need and institutional usage of GBCA, independent of study participation.
Eligibility criteria
Inclusion Criteria:
* Participant must be neurologically normal, defined as free of unstable neurologic and psychiatric disease as confirmed by a normal neurologic examination at screening
* Participant (GBCA-exposed or controls) agrees to undergo unenhanced magnetic resonance imaging (UE-MRI) of the brain at enrollment and at the end of the observation period (5 years)
* Participants should have at least 1 of the following indications: a) Medium to high risk for breast cancer or dense breasts undergoing breast cancer screening with MRI, b) Elevated prostate-specific antigen (PSA) and under active diagnostic surveillance for prostate cancer, c) Chronic liver disease (eg, liver cirrhosis limited to Child class A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) for surveillance of hepatocellular carcinoma development, d) Low-grade colorectal cancer or neuroendocrine tumor undergoing screening for liver metastases or e) Branch-duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm) undergoing imaging surveillance.
In addition, for participants in the GBCA Arms only:
* Each participant should be likely to undergo ≥5 GBCA-enhanced MR examinations with the same GBCA at least annually throughout the 5-year study duration
* Prospective participants with up to 3 well documented GBCA administrations prior to study screening are acceptable, provided that the imaging was performed with the same GBCA as the one to be prospectively used in the study. If the GBCA used cannot be identified, he/she cannot be enrolled.
For the Control Arm:
* Participants who never had and are not likely to receive any GBCA injection during the course of the study
* Each control participant must be willing to undergo UE-MRI of the brain at baseline and at Year 5. In Years 1 to 4, the control participants will undergo their clinically indicated UE-MRIs, computed tomography (CT), ultrasound, or X-ray procedures
Exclusion Criteria:
* As evidenced by history or determined in the neurologic exam at screening, concurrent neurological and/or psychiatric disease (or treatments) that could influence the results of the study's motor and cognitive tests (e.g. Cerebrovascular disease, Multiple sclerosis, Neurodegenerative disease, Malignant disease other than listed in indications, Carcinoid tumors, Epilepsy, Prior neurosurgery, Psychotic disorders or any prior psychotic episode not otherwise specified - any documented prior history of chronic schizophrenia, Remittent or current medically confirmed major depressive disorder or bipolar disorder, History of long-term major depression or bipolar affective disorder with an active episode in the past 2 to 5 years, Neurodevelopmental disorders (eg, trisomy 21), Uncontrolled severe migraine, Uncontrolled or controlled anxiety or depression within 6 months before enrollment, Screening scores of ≤24 on the MMSE and/or ≥11 on the Hospital Anxiety and Depression Scale (HADS)).
* Prior, planned, or ongoing chemotherapy or brain irradiation
* Use of concomitant medication(s) affecting neuro-cognitive or motor function
* Substance or alcohol abuse as determined by the investigator
* Alcoholic cirrhosis
* Renal disease, defined as estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2
* History of environmental/occupational/other exposure to one or more chemicals that may affect cognitive and/or motor function, including, but not limited to, heavy metals (arsenic \[As\], cadmium \[Cd\], lead \[Pb\], manganese \[Mn\], and mercury \[Hg\]), pesticides, solvents, or carbon monoxide.
* Clinical indications requiring \>1 contrast enhanced magnetic resonance imaging (CE-MRI) every 6 months
* Pregnant or nursing (lactating) women
* Presence of any metal-containing joint implants/prostheses
In addition, for participants in either of the GBCA Arms only:
\- Receipt of a GBCA or generic prior to study entry other than the specific GBCA to be administered during the course of the study.
For participants in the Control Arm only:
* Participants with any previous exposure to a GBCA.
* Participants with any contraindication to UE-MRI examinations.
Study design
Enrollment target: 2076 participants
Allocation: non_randomized
Masking: none
Age groups: adult
Timeline
Starts: 2021-03-24
Estimated completion: 2028-12-31
Last updated: 2026-01-22
Interventions
Procedure: Motor TestsProcedure: Cognitive TestsProcedure: Unenhanced-MRI of the brainProcedure: Gadolinium MeasurementsDrug: Gadoxetate disodiumDrug: Gadobenate dimeglumineDrug: GadodiamideDrug: Gadoterate meglumineDrug: GadobutrolDrug: Gadoteridol
Primary outcomes
- • Change of motor function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group (At baseline, year 5)
- • Change in cognitive function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group (At baseline, year 5)
Sponsor
Guerbet · industry
With: Bayer AG (Sponsor), Bracco (Sponsor), GEHC (Sponsor)
Contacts & investigators
ContactNathalie LE FUR, PhD · contact · nathalie.lefur@guerbet.com · +33649351166
ContactFrantz HEBERT · contact · frantz.hebert@guerbet.com · +33680249334
All locations (51)
Scottsdale Medical Imaging, LLCRecruiting
Scottsdale, Arizona, United States
Yale University School of MedicineWithdrawn
New Haven, Connecticut, United States
University of Chicago Medical CenterRecruiting
Chicago, Illinois, United States
Methodist Medical Center of IllinoisRecruiting
Peoria, Illinois, United States
Massachussets General HospitalRecruiting
Boston, Massachusetts, United States
Boston University Medical CenterTerminated
Boston, Massachusetts, United States
Beth Israel Deaconess Medical CenterWithdrawn
Boston, Massachusetts, United States
ActivMed Practices & Research, Inc.Withdrawn
Methuen, Massachusetts, United States
University of Massachusetts Memorial Medical CenterTerminated
Worcester, Massachusetts, United States
Department of RadiologyWithdrawn
St Louis, Missouri, United States
UNC School of MedicineWithdrawn
Chapel Hill, North Carolina, United States
Penn State Hershey Medical CenterRecruiting
Hershey, Pennsylvania, United States
Albert Einstein Healthcare NetworkRecruiting
Philadelphia, Pennsylvania, United States
UT Southwestern Medical CenterRecruiting
Dallas, Texas, United States
MD Anderson Cancer CenterWithdrawn
Houston, Texas, United States
University of WisconsinRecruiting
Madison, Wisconsin, United States
Hospital Santa MartaTerminated
Taguatinga, Federal District, Brazil
Liga Norte-Rio-Grandense Contra o CâncerWithdrawn
Natal, Rio Grande do Norte, Brazil
Instituto Mederi de Pesquisa e SaudeRecruiting
Passo Fundo, Rio Grande do Sul, Brazil
Hospital Moinhos de VentoRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Instituto Baía Sul de Ensino e Pesquisa (IEP)Withdrawn
Florianópolis, Santa Catarina, Brazil
CEMEC - OncológicaWithdrawn
São Bernardo do Campo, São Paulo, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio PretoRecruiting
São José do Rio Preto, São Paulo, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.Terminated
São Paulo, São Paulo, Brazil
Albert Einstein Sociedade Beneficente Israelita BrasileiraRecruiting
São Paulo, São Paulo, Brazil
CEMEC - OncológicaWithdrawn
São Bernardo do Campo, Brazil
G. Kenneth Jansz Medical Professional CorporationWithdrawn
Burlington, Ontario, Canada
Groupe Hospitalier Pitie-SalpetriereWithdrawn
Paris, France
CHU Strasbourg - Hôpital HautepierreRecruiting
Strasbourg, France
Universitaetsklinikum TuebingenActive Not Recruiting
Tübingen, Baden-Wurttemberg, Germany
Vivantes Klinikum NeukoellnRecruiting
Berlin, Germany
A.O.U. Senese Policlinico Santa Maria alle ScotteRecruiting
Siena, Siena, Italy
Azienda Ospedaliera Universitaria di TriesteRecruiting
Trieste, Trieste, Italy
Ospedale San RaffaeleRecruiting
Milan, Italy
Università Campus Bio-Medico di RomaRecruiting
Roma, Italy
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)Recruiting
Verona, Italy
BHI of Omsk region "Clinical Oncology Dispensary"Suspended
Omsk, Russia
FSBI "National medical scientific center of psychiatry and neurology n.a. V.M. Bekhterev" AdolescentSuspended
Saint Petersburg, Russia
FSBI North-West Federal Medical Research Center n.a. V.A. Almazov of MoH RFSuspended
Saint Petersburg, Russia
LLC Medical Center MartSuspended
Saint Petersburg, Russia
RSBIH "Smolensk Regional Clinical Hospital"Suspended
Smolensk, Russia
Federal State Budgetary Scientific Institution "Tomsk National Research Medical Centre of the RussiaSuspended
Tomsk, Russia
SBIH Republican Clinical Oncological Dispensary of the MoH of Republic BashkortostanSuspended
Ufa, Russia
Hallym University Chuncheon Sacred Heart HospitalWithdrawn
Chuncheon, Gangwon-do, South Korea
Chonnam National University HospitalWithdrawn
Gwangju, Gyeonggi-do, South Korea
Seoul National University Bundang HospitalRecruiting
Seongnam-si, Gyeonggi-do, South Korea
Inje University Busan Paik HospitalRecruiting
Busan, South Korea
Pusan National University HospitalRecruiting
Busan, South Korea
Chosun University HospitalRecruiting
Gwangju, South Korea
Gangnam Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, South Korea
Chung-Ang University HospitalRecruiting
Seoul, South Korea