Nervous system Nervous system
Conditions
Interventions
Carbamazepine, valproic acid and memantine HCL are registered and well-known drugs. They will be administered at a confirmed safe dosage associated with minimal and manageable side effects. Dose selec
 
Valproic acid was given in healthy volunteers in single doses up to 3000 mg, and a single dose of 1000 mg will lead to a Cmax within the therapeutic range. In an earlier study, 1000mg valproic acid sh
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Healthy female or male participants, 18 to 65 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical, surgical and psychiatric history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis. Body mass index (BMI) between 18 and 32 kg/m^2, inclusive, with a minimum weight of 50 kg. A self-reported normal or corrected vision, e.g. no strabismus. Use of any form of birth control is required for heterosexual subjects of childbearing potential who are sexually active during the study, either used by the subject or their sexual partner. Female subjects of childbearing potential are required to have a negative urine ß-hCG test at screening and pre-dose. Participants are willing to give a written informed consent (ICF) in Dutch and adhere to the lifestyle restrictions.
Exclusion criteria
Exclusion criteria: Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), and specifically hyponatremia. Clinically significant abnormalities on ECG, as judged by the investigator, including evidence of atrial fibrillation, cardiac arrythmia, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, cardiac pacemaker, an atrioventricular block or personal/family history of Brugada-syndrome. Untreated hypertension defined as SBP greater than 140 mmHg or DBP greater than 90 mmHg at screening. The measurement may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. Current diagnosis, personal history or family history of a clinically significant psychiatric disorder, including substance use disorder or suicidality, at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline of the EEG-derived cortical E/I ratio.1 Saccadic eye movement (NeuroKit and NeuroCart) Saccadic reaction time (sec) Saccadic Peak Velocity (degrees/sec) Saccadic inaccuracy (%) Smooth pursuit eye movement (NeuroKit and NeuroCart) Smooth pursuit (%) Adaptive tracking (NeuroKit and NeuroCart) Average performance (%) Body sway NeuroCart: Total sway (mm) NeuroKit: Anteroposterior root-means-square (RMS) (m/s^2) N-Back (NeuroKit and NeuroCart) Zero-back: average reaction time (msec) & accuracy (%) One-back: average reaction time (msec) & accuracy (%) Two-back: average reaction time (msec) & accuracy (%) Finger Tapping (NeuroKit and NeuroCart) Mean number of taps over 5 tests [taps/10 sec] VAS Bowdle (NeuroKit and NeuroCart) External perception (mm) Internal Perception (mm) High (mm) VAS B&L (NeuroKit and NeuroCart) Mood (mm) Alertness (mm) Calmness (mm) The roving Mismatch Negativity task (rMMN) (Neurocart) The 90% confidence interval of the ratio of effect sizes of NeuroKit and NeuroCart, of each PD endpoint per treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit Concomitant medication throughout the study at every study visit Change from baseline of: Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)) and Respiratory Rate (bpm) as per assessment schedule | — |
Countries
Netherlands
Contacts
Public ContactG.J. Groeneveld
Centre for Human Drug Research
Outcome results
None listed