Investigation in healthy volunteers and epilepsy patients
Conditions
Interventions
Product Name: [11C]metoclopramide
Pharmaceutical Form: Injection
INN or Proposed INN: metoclopramide
CAS Number: 364-62-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration nu
Sponsors
Medizinische Universität Wien, Universitätsklinik für Klinische Pharmakologie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age: =18 years old • Ability to comprehend the full nature and purpose of the study, including possible risks. • Diagnosis: o Group 1: drug resistant nonlesional focal epilepsy; suspected epileptogenic area will be delineated based on the results of phase 1 presurgical evaluation o Group 2: drug resistant epilepsy patients with epileptogenic structural lesion (except seizures associated to tumors such as glioma II); suspected epileptogenic area will be delineated based on the results of phase 1 presurgical evaluation o Group 3: Patients with focal epilepsy, who are seizure free for at least 1 year o Group 4: Patients with multiregional seizure onset zones (lesional and nonlesional subjects may be included) o Group 5: Healthy volunteers (serve as controls) • Physical examination and laboratory analysis: no presence of clinically relevant abnormal findings or values which the investigator considers may interfere with the objectives of the present study • No additional neurological or other diseases, which the investigator considers may affect the outcome of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Age:<18 years old • Unwillingness to sign the informed consent • Any abnormality found as part of the pre-treatment screening or in any of the performed laboratory tests that the investigator considers to interfere with the objectives of the study • Intake of medication during two weeks before the start of the study, which the investigator considers may affect the validity of the study. Furthermore, intake of any drugs which may cause potential harm to the subject (e.g. anticoagulation for subjects undergoing arterial cannulation) is forbidden. • Changes in medication within 2 weeks before the scan, which the investigator considers may affect the validity of the study • Any disease or condition (e.g. pregnancy, breastfeeding, evolutive tumor) which the investigator considers may affect the subject’s safety or outcome of the study • Exposure to radiation exceeding the allowed maximum foreseen by the current guidelines • History of ethanol dependence and currently abstinent • Inability to comprehend the full nature and purpose of the study • Contraindication for PET or MR imaging e.g. claustrophobia, metallic endoprosthesis, non-MR safe implants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •20 patients with DRE without structural lesion on MRI (group 1) •25 patients with DRE with epileptogenic lesion on MRI (group 2) •25 seizure free patients (group 3) •10 patients with non-focal epilepsy (Exploratory group 4 ) •20 healthy volunteers (10 per centre) ;Secondary Objective: ?To assess the safety and tolerability of [11C]metoclopramide PET ?To develop a kinetic model for quantification of [11C]metoclopramide PET data in brain ?To assess radiolabeled metabolites of [11C]metoclopramide in plasma ?To assess differences in [11C]metoclopramide metabolism between administration of a microdose (< 100 µg) and administration of a therapeutic dose (10 mg) ?To retrospectively correlate the impact of ABCB1 SNPs on brain distribution of [11C]metoclopramide;Primary end point(s): kE,brain elimination slope for radioactivity washout from the brain ;Timepoint(s) of evaluation of this end point: End of Study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • kE,brain = elimination slope of radioactivity washout from the brain efflux clearance map • 11C-metoclopramide pharmacokinetics in the blood over time • 11C-metoclopramide parent fraction = 11C-metoclopramide metabolism in epilepsy patients (and the influence of co-medication and antiepileptic drug levels on it) • K1, k2 and VT = compartmental modeling outcome parameters influx rate constant from plasma into brain (K1), efflux rate constant from brain into plasma (k2) and volume of distribution (VT) calculated from image derived input function (IDIF) (IDIF results will be validated with arterial blood sampling from a subgroup of patients) • ABCB1 single nucleotide polymorphisms • (fP) free fraction of 11C-metoclopramide fraction in plasma ;Timepoint(s) of evaluation of this end point: End of Study | — |
Countries
Austria
Contacts
Public ContactKlinische Pharmakologie
Medizinische Universität Wien
Outcome results
None listed