Can a (R)-11C-verapamil PET scan predict the epilepsy surgery outcome?

Phase 1

• Conditions: temporal lobe epilepsy; MedDRA version: 17.1Level: PTClassification code 10043209Term: Temporal lobe epilepsySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

• Registration Number: EUCTR2014-004898-16-AT
• Lead Sponsor: Medizinische Universität Wien

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04-14
• Last Update Posted: 10 December 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

•Signed informed consent
•Age: =18 years old
•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 diseases, which the investigator considers may affect the outcome of the study
•Lifetime diagnosis therapy refractory TLE, preferably hippocampal sclerosis
•Ability to comprehend the full nature and purpose of the study, including possible risks and side effects
Group 1 only: Eligible and scheduled for epilepsy surgery
Group 2a only: History of epilepsy surgery, seizure free and no AED medication since at least one year
Group 2b only: History of epilepsy surgery, seizure free, regularly on AED medication

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 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Unwillingness to sign the informed consent
•Age:<18 years old
•Any abnormality found as part of the pre-treatment screening or in any of the laboratory tests performed that the investigator considers to interfere with the objectives of the present study
•Intake of medication during two weeks before the start of the study, which the investigator considers may affect the validity of the study, due to interference with CYP3A4 or Pgp (Pgp inductors such as St. John’s wort, rifampicin or inhibitors such as esomeprazole, omeprazole, pantoprazole, lansoprazole, atrovastatin, itraconazole), or which may cause potential harm to the subject (e.g. anticoagulation)
•Changes in the medication within 2 weeks before the PET scan, which the investigator considers may affect the validity of the study
•Any disease or medical condition (e.g. pregnancy) which the investigator considers may affect the outcome of the study
•Participation in the evaluation of any drug within four weeks before the start of the study or participation in clinical studies with exposure to radiation exceeding the allowed maximum foreseen by the current guidelines (http://ec.europa.eu/energy)
•Inability to comprehend the full nature and purpose of the study
•Contraindication for MRI imaging e.g. claustrophobia, metallic endoprosthesis, stent implantation in the last months
•History of alcohol abuse.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: ?To assess Pgp function at the BBB before and after epilepsy surgery<br>?To assess epilepsy surgery outcome<br>;Secondary Objective: ?To measure regional cerebral blood flow <br>?To assess the feasibility of PET/MRI based generation of an image derived input function and metabolite analysis from venous samples as an alternative to arterial blood sampling in TLE patients <br>?To assess immunohistochemistry on resected brain tissue<br>?To assess the influence of ABCB1 single nucleotide polymorphisms on (R)-11C-verapamil distribution to the brain.<br>;Primary end point(s): ?Regional (R)-11C-verapamil influx rate constant (K1) across the BBB expressed as ml/min/cm3.<br>?Epilepsy surgery outcome according to Wieser’s classification. <br>;Timepoint(s) of evaluation of this end point: end of study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): ?MRI based calculation of cerebral blood flow (millilitres per minute) <br>?PET based image derived input function (kBq/SUV)<br>?Measurement of (R)-11C-verapamil metabolites in arterial and venous blood<br>?Determine ABCB1 single nucleotide polymorphisms (SNPs, 3435C>T, 2677G>T, 1236C>T) and the effects of genetic polymorphisms on (R)-11C-verapamil brain distribution<br>?Immunohistochemistry (resected brain tissue): % of Pgp positive labelled area<br>?Behavioral assessments including quality of life and seizure scores<br>;Timepoint(s) of evaluation of this end point: end of study