TMS to assess drug effects in epilepsy
- Conditions
- Epilepsy
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 32
1. Signed informed consent prior to any study-mandated procedure
2. Male or female subjects, 18 to 70 years of age, inclusive at screening, with generalized epileptic seizures.
3. Study participant is currently treated for epilepsy with stable doses of the following for at least 3 months:
a. Group 1: levetiracetam mono-therapy (1000 mg daily)
b. Group 2: valproic acid mono-therapy (up to and including 1000 mg daily)
4. Body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening, and with a minimum weight of 50 kg.
5. All women of child bearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment.
6. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
1. Evidence of any active or chronic disease or condition, apart from epilepsy, that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs
(systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance.
2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects.
3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
4. Abnormal findings in the resting ECG at screening defined as:
a. QTcF> 450 msec for males, or >470 for females; or < 300 msec
b. Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker.
5. Use of concomitant medications (prescription or over-the-counter [OTC]) that could interfere with the study drug or the TMS measurements, within 14 days of study drug administration, or less than 5 half-lives (whichever is longer), as judged by the investigator. This does not include the permitted medication as listed in chapter 4.4 of the protocol.
6. Participation in an investigational drug or device study within 3 months prior to first dosing.
7. History of abuse of addictive substances (alcohol, illegal substances) or current (within the last 6 months) use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillizers, or any other addictive agent.
8. Positive test for drugs of abuse at screening or pre-dose.
9. Alcohol will not be allowed from at least 24 hours before screening or pre-dose.
10. Use of tobacco or nicotine products within 24 before the dose administration.
11. A previous significant allergic reaction (urticaria or anaphylaxis) to levetiracetam.
12. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during the study, or plasma donation within 2 weeks of screening.
13. If a woman, pregnant, or breast-feeding, or planning to become pregnant during the study.
14. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
15. The subject has a history of intracranial mass lesion, hydrocephalus and/or clinically significant head injury or trauma that could increase the risk of applying TMS.
16. The subject has metal objects in brain or skull.
17. The subject has a cochlear implant or deep brain stimulation device.
18. The subject has abnormal sleeping patterns (eg, working night shifts).
19. The subject has an rMT of more than 83% of the maximum stimulator output, measured using TMS-EMG during screening.
20. History of side effects related to levetiracetam administration that would pose an unaccept
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method TMS-EMG (MEP) and TMS-EEG (TEP) response measured by:<br>- Motor evoked potential (MEP)<br>o Resting motor threshold (rMT) – (percentage of maximal output)<br>o Peak-to-peak amplitude (µV)<br>o Long intracortical inhibition (LICI) – (percentage ratio of the mean peak-to-peak amplitude of the response to the second pulse (TR) and the first conditioning pulse (CR) at each lSl (TR/CR%)), measured at a 50, 100 and 300 ms interval.<br>o Short intracortical inhibition (SlCl) - (percentage ratio of the mean peak-to-peak amplitude of the response to the second pulse (TR)<br>and an unconditioned pulse (MEP) at each lSl (TR/MEP%)), measured a1 a 2 ms interval.<br>-TMS evoked potential (TEP) using single pulse, and paired pulse TMS at 4 different lSls: 2,50, 100 and 300 ms:<br>o Amplitude of components - (pV)<br>N15<br>P30<br>N45<br>P55<br>N100<br>P180
- Secondary Outcome Measures
Name Time Method - Plasma concentrations of levetiracetam and valproic acid, and the relationship between the TMS endpoints and levetiracetam and valproic acid plasma concentrations. Valproic acid endpoints will be calculated for Group 2 only.<br>- Resting state EEG endpoints<br>o Power spectrum density (PSD), total power per band for channels Fz-Cz, Pz-O1, and Pz-O2 (see Table 2).<br>o 1/f-slope, to estimate the excitation/inhibition ratio