Effect of the Treatment of Vitamin D Deficiency in Drug-resistant Epilepsy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- Percentage reduction of the seizure frequency
研究概览
简要总结
Almost all patients with epilepsy living in the region of Paris have vitamin D deficiency, which is severe in 1/3 of the cases. The impact of this deficiency on epilepsy is unknown, despite the suggested benefits of vitamin D therapy including better seizure control and improvement of comorbidities (fatigue, anxiety, depression) in drug-resistant patients. Recommendations for vitamin D supplementation based on the serum level in the general population cannot be applied to patients with epilepsy due to interference of antiepileptic drugs in the vitamin D metabolism. Animal models, mechanisms of action studies and ecological information provide objective data for a direct antiepileptic effect of vitamin D. Human studies seem to confirm the antiepileptic effect of vitamin D but there are no controlled studies on large populations. The investigators aim to assess prospectively the effect of the treatment of vitamin D deficiency providing a high level of evidence. The investigators propose a multicentre placebo controlled randomized double-blind study, testing vitamin D supplementation against placebo in 400 drug-resistant patients to assess the short-term (3 months) and long-term (1 year) benefits on epilepsy. The investigators hypothesize that the treatment of vitamin D deficiency will result in significant reduction of seizure frequency, and improvement of comorbid symptoms as well as quality of life. The impact on the care of patients is important because better epilepsy control allows reduction of the antiepileptic drugs and side effects. This again is a key for the recovery of social and professional activities, and reduction of costs related to the disease.
详细描述
The goal of this study is to establish the effect of the compensation of vitamin D deficiency in the treatment of drug-resistant epilepsy with a high level of evidence in a large population. For that, the investigator aim to perform a controlled multicentre prospective double-blind randomized study in 400 patients.
Experimental design
After a reference period for the collection of clinical data and seizure frequency, all eligible patients will undergo biological analyses including serum vitamin D levels, calcium, creatinine and albumin. In case of proven deficiency (25(OH)D <30ng/mL), patients will be randomized into two arms:
Experimental group: drug-resistant epileptic patients supplemented with vitamin D. The vitamin D administered corresponds to the scheme described below. Control group: drug-resistant epileptic patients supplemented with placebo, administered placebo dose is equal to therapeutic dosing scheme of vitamin D. Randomization will be centralized and stratified by center (considering local disparities) and according to the results of serum level, retaining the threshold of 10ng/mL to define severe deficiency, 20 ng/mL for moderate deficiency and 30 ng/mL for slight deficiency of vitamin D.
The drug evaluated is vitamin D3 (cholecalciferol), administered in the form of oral solution (2 mL) containing 100,000 IU, manufactured by the laboratory CRINEX and marketed under the name UVEDOSE®. The therapeutic indication is the treatment and/or prophylaxis of vitamin D deficiency. The usual supplementation in adult is 1 to 2 doses per month depending on the severity of the deficiency, the maintenance ranging from 1 dose every month or every 2 to 3 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age> 15 years
- •Drug-resistant epilepsy (see definition above)
- •Having at least 6 unprovoked seizures in the previous 3 months
- •Epilepsy syndrome unequivocally established
- •Ability to reliably quantify the seizure frequency
- •Antiepileptic treatment stable for 3 months prior to inclusion
- •No vitamin D treatment in the 6 months prior to inclusion vitamin D supplemental diet
- •Medication compliance (confirmed by plasma levels if available)
- •Agreeing to participate in the study
- •Having a social insurance
- •Parental agreement if patient below the age to be able to give consent (or guardian if protected adult)
排除标准
- •Progressive brain pathology
- •Status epilepticus in the 2 years prior to inclusion,
- •epilepsy surgery planned in the current year
- •Pregnancy or breast-feeding
- •Treatments influencing the metabolism of vitamin D other than anticoagulants (rifamycin, isoniazid, ketoconazole, 5-FU fluorouracil), leucovorin)
- •Known hypersensitivity to vitamin D, patients with a history of granulomatosis (especially sarcoidosis)
- •Contraindication to treatment with Uvedose referring to the summary of product characteristics
- •Current or past hypercalcemia or situations accompanied by increased vulnerability to hypercalcemia as arrhythmia or digitalis therapy, subjects with calcium lithiasis
- •Moderate renal impairment with creatinine clearance <60 mL/mn assessed by MDRD (Modification of Diet in Renal Disease)
- •Participation in other studies of other experimental drugs within 30 days before enrollment in the study
- •Abuse of alcohol or drugs
研究组 & 干预措施
Experimental Arm
Drug resistant epilepsy patients with proved Vitamin D deficiency (Serum vitamin D level <30ng/ml) Cholecalciferol. 5 doses of cholecalciferol (100 000 IU) in 3 months than 1 dose of cholecalciferol (100 000 IU) per month during 6 months
干预措施: Cholecalciferol (Drug)
Control Arm
Drug resistant epilepsy patients with proved Vitamin D deficiency (Serum vitamin D level<30ng/ml) Placebo than cholecalciferol. 5 doses of placebo in 3 months than 5 doses of cholecalciferol (100 000 IU) in 3 months than 1 dose of cholecalciferol (100 000 IU) per month during 3 months.
干预措施: Placebo Oral (Drug)
结局指标
主要结局
Percentage reduction of the seizure frequency
时间窗: After 3 months of treatment of vitamin D deficiency
With respect to the reference period
次要结局
- Effect anxiety-depression : Hospital anxiety depression scale (HAD)(3, 6 and 12 months)
- Quality of Life in Epilepsy: (QOLIE 31) including 7 subscores: global score calculated on the basis on the mean of each subscore(3, 6 and 12 months)
- Effect on Fatigue scores : Modified Fatigue Impact Scale (M-FIS)(3, 6 and 12 months)
- Relationship between serum vitamin D levels and seizure frequency reduction after vitamin D treatment(3, 6 and 12 months.)
- Relationship between serum vitamin D level and the type and dosage of antiepileptic drugs (AED)(Baseline)
- Responder rate(3, 6 and 12 months.)
- Remission rate after Vitamin D treatment(3, 6 and 12 months.])
- Effect of Vitamin D according to epilepsy type(3, 6 and 12 months)
- Effect of Vitamin D according to epilepsy severity(3, 6 and 12 months)