目的:本研究旨在评估治疗维生素D缺乏对耐药性癫痫的影响。
方法:我们进行了多中心,双盲,安慰剂对照,随机临床试验,包括年龄≥15岁的耐药局灶性或全身性癫痫患者。25-羟基维生素D(25[OH]D)<30ng/mL的患者被随机分为接受维生素D3(胆钙化醇,100000IU,在3个月内服用5剂)或对照组(CG)接受匹配的安慰剂。在开放标签研究期间,EG患者接受100000IU/月治疗6个月,而CG患者在3个月内接受5次剂量,然后1次/月,持续3个月。监测包括癫痫发作频率(SF),25(OH)D,钙,白蛋白,肌酐检测,和标准化的疲劳量表,焦虑抑郁,和生活质量(修改后的疲劳影响量表[M-FIS],医院焦虑抑郁量表,癫痫的生活质量[QOLIE-31])在3、6和12个月。主要疗效结果是与参考期和3个月时的CG相比,SF降低的百分比。次要结果是SF和双侧强直阵挛性癫痫发作(BTCS)减少,量表分数变化,随访期间与25(OH)D的相关性。
结果:本研究纳入了88名患者(56名女性,17-74岁),每3个月的中位基线SF=16.5和≥2种抗癫痫药物,占88.6%。在75名患者(85%)中,25(OH)D<30ng/mL;其中40个随机分配给EG,34个随机分配给CG。在3个月的盲期之后,SF降低在组间没有显著差异。然而,在开放标签期间,SF显著降低(SF中位数降低30%,12个月时的应答率为33%)。BTCS减少了52%。M-FIS和QOLIE-31评分在全组水平上显著提高。SF降低与25(OH)D>30ng/mL持续>6个月相关。
结论:尽管在3个月的盲期后没有证实的效果,开放标签研究表明,长期补充维生素D3和最佳25(OH)D可能会降低SF和BTCS,对疲劳和生活质量有积极影响。这些发现需要进一步的长期研究来证实。
背景:ClinicalTrials.gov标识符:NCT03475225(03-22-2018)。
OBJECTIVE: This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy.
METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up.
RESULTS: Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months.
CONCLUSIONS: Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies.
BACKGROUND: ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).