GADOTERIDOL for Gadolinium-based contrast agent exposure — potential long-term neurocognitive and motor function changes

Inclusion criteria

• {"criterion_text":"- Participant must be an adult having reached legal majority age and less than 65 years old.\n- For the Control Arm: 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.\n- For the Control Arm: Participants matched with the population characteristics of the 2 GBCA study arms, including clinical indication for imaging, geographic region, and age-group. Additional potential risk factors (education level and sex) will be recorded and adjusted for as appropriate at the statistical analysis stage.\n- Participant must be neurologically normal, defined as free of unstable neurologic and psychiatric disease as confirmed by a normal neurologic examination at screening.\n- Participant agrees to be tested as per protocol for 5 consecutive years.\n- 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).\n- Patient affiliated to national health insurance according to local regulatory requirements, where applicable.\n- Participants should have at least 1 of the following indications: •\tMedium to high risk for breast cancer or with dense breasts undergoing breast cancer screening with magnetic resonance imaging (MRI) •\tElevated prostate-specific antigen (PSA) and under active diagnostic surveillance for prostate cancer •\tChronic liver disease (e.g., liver cirrhosis limited to Child class A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) for surveillance of hepatocellular carcinoma (HCC) development •\tLow-grade colorectal cancer or neuroendocrine tumor undergoing surveillance for liver metastases •\tBranch-duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm) undergoing imaging surveillance\n- 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.\n- In addition, for participants in the GBCA Arms only : 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.\n- For the Control Arm: Participants who never had and are not likely to receive any GBCA injection during the course of the study."}

Exclusion criteria

• {"criterion_text":"- 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. Examples include but are not limited to: •\tCerebrovascular disease •\tMultiple sclerosis •\tNeurodegenerative disease •\tMalignant disease other than listed in indications •\tCarcinoid tumors •\tEpilepsy •\tPrior neurosurgery •\tPsychotic disorders or any prior psychotic episode not otherwise specified (NOS)—any documented prior history of chronic schizophrenia •\tRemittent or current medically confirmed major depressive disorder or bipolar disorder •\tHistory of long-term major depression or bipolar affective disorder with an active episode in the past 2 to 5 years •\tNeurodevelopmental disorders (e.g., trisomy 21) •\tUncontrolled severe migraine •\tUncontrolled or controlled anxiety or depression within 6 months before enrollment •\tScreening scores of ≤24 on the Mini-Mental State Examination (MMSE) and/or ≥11 on the Hospital Anxiety and Depression Scale (HADS).\n- Clinical indications requiring >1 contrast-enhanced magnetic resonance imaging (CE-MRI) every 6 months.\n- Receipt of any investigational product or participation in any other clinical trial within 30 days prior to enrolling in this study or while enrolled in this trial.\n- Previous enrollment in this study.\n- Pregnant or nursing (lactating) women.\n- Presence of any metal-containing joint implants/prostheses.\n- In addition, for participants in either of the GBCA Arms only: Any contraindication to GBCA-enhanced MRI examinations.\n- 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.\n- In addition, for participants in the Control Arm only: Participants with any previous exposure to a GBCA.\n- In addition, for participants in the Control Arm only: Participants with any contraindication to UE-MRI examinations.\n- Prior, planned, or ongoing chemotherapy or brain irradiation.\n- Use of concomitant medication (CM)(s) affecting neuro-cognitive or motor function (an authorized exception is a single intake before the study MRI because of anxiety if administered after the motor and cognitive test evaluation): •\tRegular use of benzodiazepines or non-benzodiazepine hypnotics. Long-acting benzodiazepines (e.g., diazepam) should not be administered within 24 hours prior to cognitive testing. •\tShort/medium-acting benzodiazepines (e.g., alprazolam, lorazepam, oxazepam, temazepam), except if used chronically for sleep and on a stable dose for 8 weeks prior to Screening Visit 1 or 12 hours prior to cognitive testing •\tRegular use of anticholinergic drugs (anticholinergics for bladder control with limited cognitive effects are permitted) •\tLong-term use of corticosteroids or methotrexate, cladribine •\tRegular use of antidepressants (e.g., anticholinergic, tricyclic, monoamine oxidase inhibitors (MAOIs), norepinephrine–dopamine reuptake inhibitors (NDRIs) selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or lithium, antiepileptics and/or antipsychotic drugs: Use of antidepressants is allowed if at stable doses for 8 weeks prior to Screening Visit. Antipsychotics used on a regular basis, except for low doses of atypical antipsychotics (e.g., risperidone, aripiprazole, or quetiapine), anticonvulsants with limited cognitive effects, such as lamotrigine, pregabalin, levetiracetam for treatment of pain, and other non-epilepsy indications, are allowed as-needed basis or if used at a stable dose for 8 weeks prior to Screening Visit •\tCNS stimulants (e.g., for attention-deficit/hyperactivity disorder [ADHD])\n- Substance or alcohol abuse as determined by the investigator.\n- Alcoholic cirrhosis.\n- Any history or presence of other relevant chronic disease that prevents participation in the study or that may confound neurofunction testing.\n- Renal disease, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, calculated by using the Modification of Diet in Renal Disease (MDRD) formula or the Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.\n- 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.\n- Anticipated, current, or past conditions (medical, psychological, social, or geographical) that, in the opinion of the investigator, would compromise the participant’s safety or her/his ability to participate in the study (e.g., clinically significant vitamin B12 deficiency, folic acid deficiency, uncontrolled thyroid dysfunction from medical history)."}

Primary endpoints

• {"endpoint_text":"- The co-primary endpoints are the change from baseline to Year 5 in motor function and in cognitive function as expressed by the composite z score, defined as the weighted sum of the z scores of the individual tests. Since each of these tests is considered equally important, each test will be assigned an equal weight.","definition_or_measurement_approach":"Change from baseline to Year 5 in motor function and cognitive function measured by a composite z score (weighted sum of z scores of individual tests, each test assigned equal weight)."}

Secondary endpoints

• {"endpoint_text":"- Changes from baseline in the composite endpoint (Years 1 to 4) and in each individual test of motor and cognitive function (Years 1 to 5) will be assessed.","definition_or_measurement_approach":"Assessment of change from baseline at specified yearly time points: composite endpoint Years 1–4; individual motor and cognitive tests Years 1–5."}
• {"endpoint_text":"- Evaluation of AEs. The recording of AEs that occur after signing of the informed consent form (ICF) at Screening, will be done at baseline and at each annual visit. Signs/symptoms, onset date/time, severity, causality, seriousness, treatment and outcome will be recorded.","definition_or_measurement_approach":"Collection and recording of adverse events at baseline and each annual visit, including signs/symptoms, onset date/time, severity, causality, seriousness, treatment and outcome."}
• {"endpoint_text":"- Total gadolinium concentrations in blood plasma and urine samples collected at baseline and at each annual visit will be determined. If the CE-MRI is obtained at the same visit, the blood and urine samples will be obtained prior to imaging.","definition_or_measurement_approach":"Measurement of total gadolinium concentrations in blood plasma and urine samples in a central laboratory at baseline and each annual visit; if CE-MRI is same visit, samples taken prior to imaging."}

France

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

533

Number Of Sites

1

Number Of Participants

284

Germany

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

531

Number Of Sites

5

Number Of Participants

271

Italy

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

536

Number Of Sites

10

Number Of Participants

162

Primary sponsor

Full Name

Iqvia Rds France

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

IQVIA Limited

Responsibilities

Sponsor duties codes: 1,10,11,12,13,2,5,6,7,8,9; contact eu_clinical_trials_information@iqvia.com

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Sponsor duties codes: 1,10,11,12,13,2,5,6,7,8,9; contact eu_clinical_trials_information@iqvia.com","organisation_type":"Pharmaceutical company"}
• {"country":"","full_name":"Guerbet","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Bracco Imaging S.p.A.","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"GE Healthcare Pharma LLC","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Bayer AG","duties_or_roles":"Source of monetary support","organisation_type":""}