维生素 D 缺乏与治疗对耐药性癫痫患者癫痫发作频率和生活质量参数的影响：一项随机临床试验。

Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.

机构信息

Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France.

Epilepsy Unit, Pitié-Salpêtrière Hospital and Paris Brain Institute, Assistance Publique Hopitaux de Paris, Sorbonne University, Paris, France.

出版信息

Epilepsia. 2024 Sep;65(9):2612-2625. doi: 10.1111/epi.18050. Epub 2024 Jul 9.

DOI:10.1111/epi.18050

PMID:38980968

Abstract

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.

SIGNIFICANCE

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.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).

摘要

目的

本研究旨在评估治疗维生素 D 缺乏症对耐药性癫痫的影响。

方法

我们进行了一项多中心、双盲、安慰剂对照、随机临床试验，纳入了年龄≥ 15 岁、患有耐药性局灶性或全面性癫痫的患者。25-羟维生素 D（25[OH]D）< 30ng/mL 的患者被随机分为实验组（EG），接受维生素 D3（胆钙化醇，10 万 IU，3 个月内 5 剂）或对照组（CG）接受匹配的安慰剂。在开放标签研究中，EG 患者每月接受 10 万 IU，持续 6 个月，而 CG 患者在 3 个月内接受 5 剂，然后每月接受 1 剂，持续 3 个月。监测包括癫痫发作频率（SF）、25（OH）D、钙、白蛋白、肌酐检测以及疲劳、焦虑-抑郁和生活质量的标准化量表（改良疲劳影响量表[M-FIS]、医院焦虑和抑郁量表、癫痫生活质量[QOLIE-31]），分别在 3、6 和 12 个月时进行。主要疗效终点是与参考期和 CG 相比，3 个月时 SF 减少的百分比。次要终点是 SF 和双侧强直阵挛性发作（BTCS）减少、量表评分变化以及与随访期间 25（OH）D 的相关性。

结果

88 例患者入组（56 例女性，年龄 17-74 岁），中位基线 3 个月 SF 为 16.5，88.6%患者使用≥ 2 种抗癫痫药物。75 例（85%）患者 25（OH）D<30ng/mL，其中 40 例随机分配至 EG，34 例至 CG。在 3 个月的盲法期后，两组间 SF 减少无显著差异。然而，在开放标签期，SF 显著降低（中位 SF 减少 30%，12 个月时应答率 33%），BTCS 减少 52%。M-FIS 和 QOLIE-31 评分在全组水平上均显著改善。SF 减少与 25（OH）D>30ng/mL 且持续 6 个月以上相关。