motorische en cognitieve functie bij neurologisch normale volwassenen Long term Impact of exposure to GBCA
Conditions
Interventions
None listed
Sponsors
IQvia
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Participant must be an adult having reached legal majority age and less than 65 years old. 2. Participant must be neurologically normal, defined as free of unstable neurologic and psychiatric disease as confirmed by a normal neurologic examination at screening. 3. Participant agrees to be tested as per protocol for 5 consecutive years 4. Participant (GBCA-exposed or controls) agrees to undergo UE-MRI of the brain at enrollment and at the end of the observation period (5 years). 5. Patient affiliated to national health insurance according to local regulatory requirements, where applicable. 6. Participants should have at least 1 of the following indications: • Medium to high risk for breast cancer or with dense breasts undergoing breast cancer screening with MRI • Elevated PSA under active diagnostic surveillance of prostate cancer • 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 • Low-grade colorectal cancer or neuroendocrine tumor undergoing surveillance for liver metastases • Branch-duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size
Exclusion criteria
Exclusion criteria: 1. 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: • 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 (NOS)*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 =11 on the HADS. 2. Prior, planned, or ongoing chemotherapy or brain irradiation. 3. Use of concomitant medication(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): • Regular use of benzodiazepines or non-benzodiazepine hypnotics. Long-acting benzodiazepines (eg, diazepam) should not be administered within 24 hours prior to cognitive testing. • Short/medium-acting benzodiazepines (eg, 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. • Regular use of anticholinergic drugs (anticholinergics for bladder control with limited cognitive effects are permitted). • Long-term use of corticosteroids or methotrexate, cladribine. • Regular use of antidepressants (eg, anticholinergics, tricyclics, monoamine oxidase inhibitors [MAOIs], norepinephrine-dopamine reuptake inhibitors [NDRIs], selective serotonin reuptake inhibitors [SSRIs], serotonin and norepinephrine reuptake inhibitors [SNRIs], or lithium, anti-epileptics, 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 • CNS stimulants (eg, for ADHD). 4. Substance or alcohol abuse as determined by the investigator. 5. Alcoholic cirrhosis. 6. Any history or presence of other relevant chronic disease that prevents participation in the study or that may confound neurofunction testing. 7. 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. 8. History of environmental/occupational/other exposure to one or mor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| o-Primary Endpoint to Assess Motor Function One co-primary endpoint is the change from baseline to year 5 in motor function as expressed by 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. The 4 tests to assess motor functions for the specific motor function domains (described in detail in Appendix 1) are the Nine Hole Peg Test (NHPT), the Finger Tapping Test (FTT), the Single Leg Stance Test (SLST), and the Timed Up and Go (TUG) test. 3.3.2 Co-Primary Endpoint to Assess Cognitive Function The other co-primary endpoint is the change from baseline to year 5 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 the tests is considered equally important, each test will be assigned an equal weight. The 3 tests to assess cognitive functions for the specific 5 cognitive function domains (described in detail in the separate Motor Function and Cognitive Testing Appendix) are the | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes from baseline in the composite endpoints (Years 1 to 4) and in each individual test of motor and cognitive function (Years 1 to 5) will be assessed. Additional secondary endpoints include: • Evaluation of adverse events. 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 and end date, severity, causality, seriousness, treatment, and outcome, will be recorded. • 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. | — |
Countries
Netherlands
Outcome results
None listed