epilepsy P-glycoprotein flumazenil pharmacoresistance epilepsie P-glycoproteine flumazenil farmacoresistentie
Conditions
Interventions
2x [11C]flumazenil- and 2x [15O]water PET scan with one gift of Tariquidar in between.
Sponsors
VU University Medical Center and Stichting Epilepsie Instellingen Nederland (SEIN
Eligibility
Inclusion criteria
Inclusion criteria: Investigational group: 1. Diagnosis of pharmacoresistant TLE, based on clinical evaluation and (video-) EEG; 2. Age between 18-60 years; 3. Normal liver function tests; 4. Normal full blood count; 5. Weight >50 kg; 6. All subjects have to be willing and able to give informed consent (written). If necessary, healthy volunteers will be included: 1. Age between 18-50 years; 2. Good physical health evaluated by medical history, physical (including neurological) examination and screening laboratory tests; 3. Weight >50 kg; 4. RDC (Research Diagnostic Criteria) diagnosis never mentally ill; 5. Written informed consent of each subject.
Exclusion criteria
Exclusion criteria: 1. Any clinical significant abnormality of any clinical laboratory test; 2. Any subject who has received any investigational medication within 30 days prior to the start of this study, or who is scheduled to receive an investigational drug; 3. Any subject who has been prescribed a benzodiazepine preparation within 1 month prior to the start of this study; 4. Major psychiatric or neurological disorder other than TLE with or without a known substrate; 5. History of alcohol and/or drug abuse; 6. History of coagulation problems; 7. Use of non-steroid anti-inflammatory drugs or drugs known to interfere with the P-gp, other than AEDs; 8. Abnormalities on MRI other than temporal localised pathology, that is the cause and/or effect of the TLE, and/or abnormalities on MRI other than white matter changes or an incidental small lacunar lesion without clinical diagnosis; 9. Blood donation or substantial blood loss within 3 months before the scan day; 10. Metal objects in or around the body.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The influence of P-gp function at the BBB on flumazenil binding to the GABAA-receptor in pharmacoresistant patients with TLE. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The effect of tariquidar on the cerebral blood flow (CBF). If there is an effect of tariquidar on CBF; 2. The effect of blood flow in the brain on [11C]flumazenil uptake. If flumazenil is a substrate for P-gp; 3. Quantification of the upregulation of P-gp by TLE, by comparing pharmacoresistant patients with TLE with healthy volunteers. | — |
Contacts
Public ContactJ.C. Reijneveld
P.O. Box 7057
Outcome results
None listed