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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
Author(s) -
Jia Jianping,
Wei Cuibai,
Liang Junhua,
Zhou Aihong,
Zuo Xiumei,
Song Haiqing,
Wu Liyong,
Chen Xiaochun,
Chen Shengdi,
Zhang Junjian,
Wu Jiang,
Wang Kai,
Chu Lan,
Peng Dantao,
Lv Peiyuan,
Guo Hongzhi,
Niu Xiaoyuan,
Chen Yingzhu,
Dong Wanli,
Han Xiujie,
Fang Boyan,
Peng Mao,
Li Dan,
Jia Qian,
Huang Liyuan
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.04.010
Subject(s) - dementia , vascular dementia , clinical dementia rating , placebo , randomized controlled trial , medicine , population , clinical trial , cognitive decline , disease , physical therapy , psychology , pathology , alternative medicine , environmental health
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. 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.