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: µg microgram(s)
Concentration type: up to
Concentration nu
Sponsors
CEA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Age: =18 years old=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 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 • Subject participating in a parallel drug study/ radiotraceur <1year • Vulnerable person (person under guardianship, curatorship)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess via 11C-metoclopramide PET the P-gp function at the blood brain barrier of patients with epilepsy ;Secondary Objective: •To evaluate the sensitivity of 11C-metoclopramide to localize epileptogenic foci in DRE •To study the brain kinetics of 11C-metoclopramide in focal lesions of patients with DRE and healthy controls •To address the hypothesis of heterogeneity of P-gp function between seizure onset zones in patients with multiregional epilepsy (investigate the possible presence of individual drug-resistant foci). •To assess the feasibility to discriminate drug resistant from drug sensitive epileptogenic foci •To test a compartmental model for quantification of 11Cmetoclopramide brain PET in epilepsy patients as well as the implementation of an image derived input function (IDIF) •To assess radiolabeled metabolites of 11C-metoclopramide in plasma as and measure therapeutic drug levels •To retrospectively correlate the impact of ABCB1single nucleotide polymorphisms (SNPs) on brain distribution of 11C-metoclopramide •To measure the plasma free fraction (fP) 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 map = Parametric approach: radioactivity washout from the brain efflux clearance calculated for each pixel and expressed as 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/epileptic focus (K1), efflux rate constant from brain/epileptic focus 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
France
Contacts
Public ContactClinicaltrials vigilance
CEA
Outcome results
None listed