A randomized, double-blind, two-way cross-over study to determine the effects of levetiracetam on corticospinal excitability in patients with treatment-controlled epilepsy, as measured by single and paired pulse TMS-EMG and TMS-EEG

Recruiting

Conditions: Epilepsy
10039911

Registration Number: NL-OMON49353

Lead Sponsor: Centre for Human Drug Research

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 32

Inclusion Criteria

1. Signed informed consent prior to any study-mandated procedure
2. Male or female subjects, 18 to 54 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 30 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.

Exclusion Criteria

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 this 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>TMS-EMG (MEP) and TMS-EEG (TEP) response measured by:<br /><br>- Motor evoked potential (MEP)<br /><br>o Resting motor threshold (rMT) - (percentage of maximal output)<br /><br>o Peak-to-peak amplitude (µV)<br /><br>o Long intracortical inhibition (LICI) - (percentage ratio of the mean<br /><br>peak-to-peak amplitude of the response to the second pulse (TR) and the first<br /><br>conditioning pulse (CR) at each ISI (TR/CR%)), measured at a 50 and 100 ms<br /><br>interval.<br /><br>o Short intracortical inhibition (SICI) - (percentage ratio of the mean<br /><br>peak-to-peak amplitude of the response to the second pulse (TR) and an<br /><br>unconditioned pulse (MEP) at each ISI (TR/MEP%)), measured at a 2 ms interval.<br /><br>- TMS evoked potential (TEP) using single pulse, and paired pulse TMS at 3<br /><br>different ISIs: 2, 50 and 100 ms:<br /><br>o Amplitude of components - (µV)<br /><br>N15<br /><br>P30<br /><br>N45<br /><br>P55<br /><br>N100<br /><br>P180</p><br>

Secondary Outcome Measures