Effect of Small Changes in Plasma Valproic Acid Concentration on the Photoparoxysmal Response
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Difference in SPR During Placebo and VPA Infusions
研究概览
简要总结
We are trying to learn if small changes in the amount of a valproate in the blood (given through an IV) will change the way the brain reacts to flashing lights.
详细描述
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.
Specific Aims
- 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.
Hypothesis
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients
- •Aged 15 to 65 years
- •Patients with a diagnosis of epilepsy for which they are either taking up two AEDs, not including VPA/divalproex, or no AEDs
- •Patients with a reproducible IPS-induced photo-paroxysmal responses of at least 7 SPR-EEG units as measured at two different time points in the day (pm screening Study Visit 1 and am of Visit 2).
- •Are in good health (with the exception of epilepsy).
- •Able and willing to provide written informed consent.
排除标准
- •Patients not exhibiting a photo-paroxysmal-EEG response
- •Patients with active psychogenic seizures
- •Women who are pregnant or lactating
- •Women of reproductive potential who do not agree to use effective birth-control methods during the study and for one week after receiving study drug.
- •Patients taking any dosage form of VPA/divalproex within 4 weeks prior to the study
- •Patients taking more than two concomitant AEDs
- •Patients with any clinically significant laboratory abnormality, which in the opinion of the investigator, will exclude the patient from the study
- •Patients who are suffering from active liver disease indicated by abnormal liver function tests greater than three times the upper limit of normal (AST and ALT), patients with porphyria, or patients with a family history of severe hepatic dysfunction
- •Patients with a history of alcoholism, drug abuse, or drug addiction (within the past 12 months)
- •Patients with a history of sensitivity or allergic reaction to valproate / divalproex
- •Patients who have a medical history which would contraindicate sodium valproate (VPA) administration
- •Patients who have participated in any other trials involving an investigational product or device within 30 days of screening.
- •Patients with clinically significant ECG abnormalities, as judged by the PI, at screening visit
- •Patients with such poor intravenous access that the insertion of two intravenous catheters (one for sodium valproate infusion and one, in a contralateral arm vein, for serial blood sampling) for a 12-hour period is not possible.
- •Patients who received benzodiazepines within one week of study initiation
- •Status epilepticus within one year of screening
- •Generalized tonic-clonic seizure within 24 hours of photic stimulation procedure
研究组 & 干预措施
Placebo then Valproic Acid (VPA)
all patients will have placebo on day 1 and VPA infusion on day 2
干预措施: Valproic Acid (Drug)
Placebo then Valproic Acid (VPA)
all patients will have placebo on day 1 and VPA infusion on day 2
干预措施: Placebo (Drug)
结局指标
主要结局
Difference in SPR During Placebo and VPA Infusions
时间窗: At the start of EEG monitoring/drug infusion, and on an hourly basisfor 12 hours
standard photosensitive range (SPR) Each participant is exposed to intermittent photic stimulation at 14 predetermined frequencies in order to detect changes in response around typical upper and lower frequency thresholds (e.g., 2 Hz, 5 Hz, 8Hz, 10 Hz, etc.). Each flash frequency that elicits a photosensitive response is considered one "step", and the result is transformed into a metric called the standardized photosensitive range (SPR). The SPR ranges from 0 to 14, where each point represents the number of flash frequencies that elicited a photosensitive response.
次要结局
未报告次要终点
研究者
Bassel Abou-Khalil
Principal Investigator
Vanderbilt University Medical Center