Open Label Single Center Trial Evaluating the Efficacy and Safety of Diazepam in GAD65 Associated Epilepsy
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Mayo Clinic
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in seizure frequency
研究概览
简要总结
The purpose of this study is to determine whether diazepam reduces the frequency of seizures in GAD65 antibody associated epilepsy.
详细描述
GAD65 is an intracellular enzyme that plays a key role in the conversion of glutamate to gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. Benzodiazepines augment the sensitivity of the GABA-A receptor to GABA, prolonging its inhibitory effect, perhaps enhancing the potential for neural inhibition in conditions in which GABA is depleted.
GAD65 antibodies have been identified in a subset of patients with drug resistant focal epilepsy and limbic encephalitis. While it has not been definitively determined that these antibodies cause GAD65 inhibition and GABA depletion directly, diazepam, a common benzodiazepine, has been established as a mainstay of therapy for stiffperson's syndrome, a condition that is commonly associated with GAD65 antibody positivity. Given these observations, diazepam has been used by the investigators in a small number of patients with intractable epilepsy in the setting of GAD65 antibody positivity, with some encouraging anecdotal results with one patient being rendered seizure free for three years.
The purpose of this study is to generate prospective data on use of diazepam in patients with epilepsy related to high-titer GAD65 antibody positivity.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •High-titer serum GAD65 positivity > 20 nmol/L High-titer serum GAD65 IgG seropositivity titer >20 nmol/L and/or CSF GAD65 seropositivity titer > 0.02 nmol/L.
- •Drug-resistant focal epilepsy, having failed 2 previous anti-seizure medications.
- •Stable treatment for the 1 month prior to enrollment.
- •Patients must be able to give informed consent or have an appropriate representative available to do.
排除标准
- •Alternative etiology for epilepsy.
- •Already on another benzodiazepine.
- •On a regularly scheduled opiate.
- •Co-existing antibodies associated with seizures.
- •Pregnancy or breast feeding.
研究组 & 干预措施
GAD65 Associated Epilepsy
Subjects diagnosed with GAD65 associated epilepsy, serum high-titer GAD65 positivity, trialed and failed at least 2 anti-seizure medications, at least 4 seizures per month will be started on diazepam.
干预措施: Diazepam (Drug)
结局指标
主要结局
Change in seizure frequency
时间窗: Baseline, 3 months
Median percentage change in the mean monthly frequency of seizures as measured by patient recorded seizure frequency
次要结局
未报告次要终点
研究者
Kelsey M. Smith
Principal Investigator
Mayo Clinic