Effect of Valproic Acid Concentration on Photic Response
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Effect of Small Changes in Plasma Valproic Acid Concentration on the Photoparoxysmal Response|
- Analysis of total change in SPR from baseline to highest VPA conc., for each patient, averaged across patients, determines overall efficacy of VPA. [ Time Frame: At the start of EEG monitoring/drug infusion, and also on an hourly basis thereafter ] [ Designated as safety issue: No ]
|Study Start Date:||December 2007|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
|Active Comparator: VPA||
Drug: Valproic Acid
The investigators will utilize intravenous sodium valproate at visit 3. Dosage will be individualized to each patient's body weight, age, and hepatic-enzyme-inducing status. Intravenous Na VPA dose predictions will be based upon population VPA pharmacokinetic parameters (Dutta 2003).
Other Name: Depakote
|Placebo Comparator: placebo||
Each patient will have a placebo-infusion (with 0.9% NS or D5W) of 12-hour duration at visit 2.
Photosensitive epilepsy is a form of epilepsy that is considered to have a genetic basis in most instances. It is a reflex type of epilepsy. Patients with this condition exhibit epileptic activity patterns (called photoparoxysmal response-PPR) on their EEG during intermittent photic stimulation with certain flash frequencies.
- To determine the extent of the pharmacodynamic effect of small changes in total and free VPA concentration via constant infusion of intravenous sodium valproate within the same photosensitive epilepsy patient.
- To determine the change in total and free VPA concentration required to achieve maximal effect on PPR in patients with photosensitive epilepsy.
- Valproic acid (VPA) demonstrates differential pharmacodynamic effect on PPR with small changes in VPA concentration (5-20 mg/L changes in total, or 0.5 to 2 mg/L changes in free VPA) within the same patient. In essence, the VPA concentration-response curve in patients with photosensitive epilepsy is relatively steep.
- Intravenously-administered VPA will demonstrate a reduction in standard photosensitive range (SPR) or abolition of PPR for at least 80% of patients studied, when the entire range of free VPA concentrations is considered.
Photosensitivity, defined as a PPR on intermittent photic stimulation (IPS), is found in approximately 5% of all epileptic patients. Markedly photosensitive patients are usually sensitive to IPS within clearly defined limits of flash frequency (mostly between 10-30 Hz). This photosensitivity range, the difference between the highest and lowest flash rates that consistently elicit a photoparoxysmal response (PPR), can be used as a quantitative measure of photosensitivity.
Administration of some antiepileptic drugs (AEDS) can diminish or even abolish PPR. With a standard set of tested frequencies, a standard photosensitive range (SPR) can be used to measure drug effect on photosensitivity. Combined with blood level monitoring, the model offers information about actual pharmacodynamic effect as measured with IPS related to the changes in blood levels.
The standardized IPS procedure includes delivery of short (5 second-) trains of flashes. The stimulation starts with the lowest frequencies (which usually do not produce a PPR) only up to the limits of the photosensitivity range (the threshold frequencies for which the patient shows an epileptiform EEG response). After that the stimulation starts again with the highest frequencies (which also do not produce a PPR) down to the frequency that produces a definite PPR.
The photic stimulator will be manually controlled for all stimulations in order to abort the stimulation when a clear PPR is elicited. With all stimulations, there is simultaneous recording of the EEG and direct observation of the patient for clinical changes. With all the safety measures in place, the likelihood of provoking prominent clinical seizures is extremely low.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00609245
|United States, Missouri|
|The Comprehensive Epilepsy Care Center for Children & Adults|
|Chesterfield, Missouri, United States, 63017|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Bassel Abou-Khalil, MD||Vanderbilt University|
|Principal Investigator:||William Rosenfeld, MD||The Comprehensive Epilepsy Care Center for Children & Adults|
|Principal Investigator:||Dorothee Kasteleijn-Nolst Trenite, MD, PhD||The Comprehensive Epilepsy Care Center for Children & Adults|