The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial

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• 作者：Jianping Jia^a ; ^b ; ^{jjp@ccmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Cuibai Wei^a ; Junhua Liang^a ; Aihong Zhou^a ; Xiumei Zuo^a ; Haiqing Song^a ; Liyong Wu^a ; Xiaochun Chen^c ; Shengdi Chen^d ; Junjian Zhang^e ; Jiang Wu^f ; Kai Wang^g ; Lan Chu^h ; Dantao Pengⁱ ; Peiyuan Lv^j ; Hongzhi Guo^k ; Xiaoyuan Niu^l ; Yingzhu Chen^m ; Wanli Dongⁿ ; Xiujie Han^o ; Boyan Fang^p ; Mao Peng^a ; Dan Li^a ; Qian Jia^a ; Liyuan Huang^a
• 关键词：DL-3-n-Butylphthalide ; Vascular cognitive impairment without dementia ; Cerebral small vessel disease ; Randomized controlled trial ; Multicentre study
• 刊名：Alzheimer's & Dementia
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：12
• 期：2
• 页码：89-99
• 全文大小：784 K

文摘

Vascular cognitive impairment without dementia is very common among the aged and tends to progress to dementia, but there have been no proper large-scale intervention trials dedicated to it. Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl-3-n-butylphthalide (NBP) is effective for cognitive impairment of vascular origin.

Methods

In this randomized, double-blind, placebo-controlled trial, we enrolled patients aged 50–70 years who had a diagnosis of subcortical Vascular cognitive impairment without dementia at 15 academic medical centers in China. Inclusion criteria included a clinical dementia rating ≥0.5 on at least one domain and global score ≤0.5; a mini-mental state examination score ≥20 (primary school) or ≥24 (junior school or above); and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. Patients were randomly assigned to NBP 200 mg three times daily or matched placebo (1:1) for 24 weeks according to a computer-generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 24 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and the per protocol population.

3">Results

This study enrolled 281 patients. NBP showed greater effects than placebo on ADAS-cog (NBP change −2.46 vs. placebo −1.39; P = .03; ITT) and CIBIC-plus (80 [57.1%] vs. 59 [42.1%] patients improved; P = .01; ITT). NBP-related AE were uncommon and primarily consisted of mild gastrointestinal symptoms.

Discussion

Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.