Objective

To evaluate the effects of oral pharmacological cannabidiol (CBD) on seizures, side effects, quality of life, behavior, mood, and sleep in children with drug-resistant epilepsy (DRE) during a phase II, prospective, open-label clinical study.

Methods

During a phase II expanded access program (EAP) study to evaluate the safety and efficacy of using cannabidiol (CBD) for the long-term treatment of children with drug-resistant epilepsy, secondary outcome measures were also performed, including quality of life (QOLCE), behavior (aberrant behavior checklist ABC), and sleep (children’s sleep habit questionnaire, CSHQ). Participants between the ages of 2 and 16 years of age with drug-resistant epilepsy (n = 35) were included in this EAP. Primary outcomes included change in parent-recorded seizure frequency relative to baseline, as well as the safety and tolerability over the course of 24 months of CBD treatment. Secondary outcomes observed in the first 12 months included changes in child behavior, and cognitive function, and sleep quality.

Results

The median change in overall seizure frequency decreased from baseline (n = 33) by −61.3% ([n = 33], Inter Quartile Range (IQR): 43–88%) at month 3, −62.9% at month 6 ([n = 29], IQR: 48–92%), −74.7% at month 12 ([n = 29], IQR: 64–96%), and finally −83.7% ([n = 28], IQR: 68–100%) at the conclusion of 24 months of treatment. Seven (20%) of the 35 patients enrolled withdrew from treatment and observation by month 24: 2 failed inclusion criteria at baseline, 4 due to lack of treatment efficacy, and 1 was lost to follow-up. The 12-month recording of secondary measures revealed a significant improvement in Irritability (-39.4%, [n = 28], ABC), Hyperactivity (-45.4%, [n = 28], ABC), Cognition in Quality of Life (+14.2%, [n = 28], QOLCE), Behavioral function (+14.7%, [n = 28], QOLCE), General Health (+14.7%, [n = 28], QOLCE), Sleep duration (–33.9%, [n = 28], CSHQ), Daytime sleepiness (–23.8%, [n = 28], CSHQ), and nocturnal arousals (-36.2%, [n = 28], CSHQ).

Significance

The results of this phase II open-label study demonstrate that pharmacological CBD significantly reduces seizure frequency, and improves QOL, behavior deficits, and sleep disruption, in children with drug-resistant epilepsy. The results also suggest that CBD is efficacious in controlled seizures over a 2-year period in childhood DRE.

中文翻译：

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参加一项大麻二酚前瞻性、开放标签临床研究的儿科患者的癫痫发作频率、生活质量、行为、认知和睡眠

 客观的

在一项 II 期、前瞻性、开放标签临床研究中，评估口服药理学大麻二酚 (CBD) 对耐药性癫痫 (DRE) 儿童癫痫发作、副作用、生活质量、行为、情绪和睡眠的影响。

 方法

在一项旨在评估使用大麻二酚 (CBD) 长期治疗耐药性癫痫儿童的安全性和有效性的 II 期扩展准入计划 (EAP) 研究中，还进行了次要结果测量，包括生活质量 (QOLCE) ）、行为（异常行为检查表 ABC）和睡眠（儿童睡眠习惯问卷，CSHQ）。本 EAP 包括年龄在 2 岁至 16 岁之间的耐药性癫痫参与者 ( n = 35)。主要结局包括家长记录的癫痫发作频率相对于基线的变化，以及 CBD 治疗 24 个月过程中的安全性和耐受性。前 12 个月观察到的次要结果包括儿童行为、认知功能和睡眠质量的变化。

 结果

第 3 个月时，总体癫痫发作频率的中位变化较基线 ( n = 33) 下降了 -61.3%（[ n = 33]，四分位数范围 (IQR)：43–88%），第 6 个月时下降了 -62.9%（[ n = 29]，IQR：48–92%），第 12 个月时为 −74.7%（[ n = 29]，IQR：64–96%），最后为 −83.7%（[ n = 28]，IQR：68– 100%）在24个月的治疗结束时。到第 24 个月时，35 名患者中有 7 名 (20%) 退出治疗和观察：2 名患者在基线时未达到纳入标准，4 名患者由于缺乏治疗效果，1 名患者失访。 12 个月的次要测量记录显示，烦躁（-39.4%，[ n = 28]，ABC）、多动（-45.4%，[ n = 28]，ABC）、生活质量认知（+ 14.2%，[ n = 28]，QOLCE)，行为功能 (+14.7%，[ n = 28]，QOLCE)，一般健康状况 (+14.7%，[ n = 28]，QOLCE)，睡眠持续时间 (–33.9% ，[ n = 28]，CSHQ），日间嗜睡（–23.8%，[ n = 28]，CSHQ）和夜间觉醒（-36.2%，[ n = 28]，CSHQ）。

 意义

这项 II 期开放标签研究的结果表明，药理学 CBD 显着降低了耐药性癫痫儿童的癫痫发作频率，并改善了生活质量、行为缺陷和睡眠中断。结果还表明，CBD 在儿童 DRE 的两年时间内有效控制癫痫发作。