This study is a postmarketing requirement jointly carried out by four NDA holders (Bayer AG, Bracco, GE Healthcare and Guerbet) and the CRO IQVIA.
The study aims to create detailed images of the organs and tissue of the human body during x-ray, CT-scan or MRI investigations, doctors are using contrast media (a kind of dye) which can be given to patients by injection into a blood vessel or by mouth.
In this study researchers want to find out whether so called gadolinium-based contrast agents (GBCAs) have an effect on body movement and mental skills when given to participants multiple times within 5 years.
The study plans to enroll about 2076 participants suffering from a condition for which they are likely to have at least annually a MRI or another imaging examinations. Only adults up to 65 years will be considered to join this study. During the study duration of 5 years participants will receive annually a MRI or other imaging tests (such as CT-scan, x-ray) and will visit the study doctor at least 7 times for physical examinations, laboratory investigations and tests on body movement and mental skills.
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.
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
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
Parallel
Motor Tests
Procedure/SurgeryTo assess motor function annually
Cognitive Tests
Procedure/SurgeryTo assess cognitive function annually
Unenhanced-MRI of the brain
Procedure/SurgeryThe UE-MRI of the brain will be performed at baseline and at the year 5 visit in order to exclude presence of a significant MRI abnormality
Gadolinium Measurements
Procedure/SurgeryBlood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration
Gadoxetate disodium
DrugAdministered as defined by the treating physician as part of routine clinical practice
Gadobenate dimeglumine
DrugAdministered as defined by the treating physician as part of routine clinical practice
Gadodiamide
DrugAdministered as defined by the treating physician as part of routine clinical practice
Gadoterate meglumine
DrugAdministered as defined by the treating physician as part of routine clinical practice
Gadobutrol
DrugAdministered as defined by the treating physician as part of routine clinical practice
Gadoteridol
DrugAdministered as defined by the treating physician as part of routine clinical practice
Change of motor function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
Change in cognitive function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
Change from baseline in the composite endpoints (motor and cognitive) at each of the post-baseline time points (Years 1 to 4) in GBCA-exposed participants as compared to controls.
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
Change from baseline for each of the individual tests (motor and cognitive) at each of the post-baseline time points (Years 1 to 5) in GBCA-exposed participants as compared to controls.
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
Number of participants with adverse events
Total Gd concentrations (as measured in a central laboratory) in blood and urine samples taken from exposed and control participants at the time of the annual visit
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Guerbet
Lead sponsor
Bayer AG (Sponsor)
Collaborator
Bracco (Sponsor)
Collaborator
GEHC (Sponsor)
Collaborator
