Department of Neuroscience, Angers University Hospital, France.
Trials. 2011 Oct 20;12:230. doi: 10.1186/1745-6215-12-230.
Current treatments for Alzheimer's disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine.
The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer's Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone.
The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD.
ClinicalTrials.gov number, NCT01409694.
目前针对阿尔茨海默病和相关疾病（ADRD）的治疗方法都是对症治疗，只能暂时减缓 ADRD 的发展。未来的护理选择依赖于多靶点药物治疗，这种治疗方法可以同时针对导致神经退行性变的多种病理生理过程。我们假设，将美金刚与维生素 D 联合使用可能对 ADRD 具有神经保护作用，从而限制神经元丢失和认知能力下降。本试验旨在比较口服维生素 D3（胆钙化醇） 24 周后与安慰剂对接受美金刚治疗的中度 ADRD 患者认知功能变化的影响。
AD-IDEA 试验是一项单中心、双盲、随机、安慰剂对照、意向治疗、优效性试验。入组患者为年龄 60 岁及以上、患有中度 ADRD（即简易精神状态检查[MMSE]评分 10-20 分）、维生素 D 缺乏（即血清 25-羟维生素 D[25OHD]＜30ng/ml）、血钙正常（即血清钙＜2.65mmol/L）且在入组时未接受任何抗痴呆治疗的患者。所有参与者均接受美金刚 20mg 每日一次治疗 -4 周内逐渐增加 5mg 滴定剂量-，并随机分为两种治疗方案之一：胆钙化醇（每 4 周一次，10 万 IU 口服液）或安慰剂（以相同速度给药）。共招募 120 名参与者，治疗持续 24 周。主要观察指标为使用阿尔茨海默病评估量表-认知评分评估认知功能变化。次要观察指标为其他认知评分（MMSE、额叶评估量表、连线测试 A 和 B）变化、功能表现变化（日常生活活动量表和四项工具性日常生活活动量表）、姿势和步态（计时起立行走测试、五次坐站测试、行走时空分析）以及治疗依从性和耐受性的组间比较。这些结果在基线、12 周和 24 周时进行评估，同时还评估了血清 25OHD、钙和甲状旁腺激素浓度。
美金刚联合维生素 D 可能代表治疗 ADRD 的一种新的多靶点治疗类别。AD-IDEA 试验旨在提供其在限制 ADRD 认知和功能下降方面疗效的证据。
ClinicalTrials.gov 编号，NCT01409694。
