The Efficacy of DL-3-n-butylphthalide (DL-NBP) on the Cognitive Function and Vascular Regulation in Patients With Mild Vascular Dementia (VaD) Caused by Subcortical Ischemic Vascular Disease (SIVD)
试验速览
- 阶段
- 不适用
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Symbol Digit Modalities Test (SDMT) at endpoint and change from baseline
研究概览
简要总结
This is a 48-week, double-blind, randomized, placebo-controlled study. Sixty-four patients are randomly assigned to take NBP (600mg per day) or placebo for 48 weeks, with 32 patients in each treatment group. Anti-dementia treatment-naive patients meet the inclusion/exclusion criteria are enrolled.
Patients are assigned to NBP will take 200mg tid daily. Patients are visited at baseline, as well as 4, 12, 24, 36, 48weeks after baseline. Safety data is recorded until an additional 30 days after the last treatment (48 weeks).
The primary outcomes include cognitive function and activities of daily living (ADL). All subjects are assessed at baseline, 4w, 12w,24w, 36w intermittent visit and 48w endpoint with the Auditory Verbal Learning Test (AVLT), the Brief Visuospatial Memory Test-Revised (BVMT-R), the Symbol Digit Modalities Test (SDMT), the Trail Making Test-A/B (TMT-A/B), the Benton Judgment of Line Orientation (JLO), the verbal fluency test, the Boston Naming Test (BNT), the Controlled Oral Word Association Test (COWAT), the Stroop test, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the ADL. The secondary outcomes include the global function and behavioral and psychological symptoms of dementia (BPSD), which are evaluated with the Clinical Dementia Rating (CDR) and the Neuropsychiatric Inventory (NPI), respectively. Independent raters who are blinded to patients' distribution are assigned to assess the participants.
The exploratory outcomes are markers of vascular regulation, including circulating endothelial progenitor cells (EPCs), white matter hyperintensities (WMH) on MRI, cerebral blood flow (CBF) measured with transcranial Doppler (TCD) and arterial spin labeling (ASL) MRI, and parameters of carotid duplex ultrasonic (CDU). In addition, apolipoprotein E (APOE) polymorphism and plasma biomarkers are also detected.
Safety are assessed at each visit.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients meet the criteria of major neurocognitive disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5);
- •Patients aged with 50-80 years, years of education no less than 3, an MMSE range of 15~26, an MoCA < 26, an Hamilton Depression Scale (HAMD) < 17;
- •The MRI (one research dedicated machine 3.0 T) features satisfy subcortical small vessel disease, including (1) multiple (>=3) supratentorial subcortical lacunes (3-20 mm in diameter), with/without white matter hyperintensities (WMH) of any degree; (2) moderate to severe WMH (score>= 2 according to the Fazekas rating scale in either periventricular region or deep white matter) with/without lacunes; (3) one or more strategically located subcortical small infarcts in the deep grey matters;
- •Patients or legal representative should sign the informed consent and have a reliable caregiver.
排除标准
- •Cognitive impairment caused by other central nervous system diseases, such as AD, dementia with Lewy body, frontal-temporal lobe degeneration, etc;
- •Cognitive impairment due to other conditions, such as severe depression, vitamin B 12 deficiency, abnormal thyroid function, etc;
- •Alcoholism, drug abuse or other conditions influenced the evaluation of cognition;
- •Patients unable to undertake MRI assessment.
- •Patients with a history of other severe disease such as epilepsy, myocardial infarction or heart failure will be excluded;
- •Administration of other investigational drugs, psychotropic drugs, drugs with psychiatric side effects, and oral anticoagulants are not allowed
研究组 & 干预措施
Placebos
Placebo, soft capsule, 200mg Tid, po, for 48 weeks.
干预措施: Placebos (Drug)
NBP
DL-3-n-butylphthalide (NBP), soft capsule, 200mg Tid, po, for 48 weeks.
干预措施: NBP (Drug)
结局指标
主要结局
Symbol Digit Modalities Test (SDMT) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
SDMT is used to assess information processing speed. Higher score indicates better performance.
Boston Naming Test (BNT) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
BNT is used to evaluate language function. Higher score indicates better performance.
Montreal Cognitive Assessment (MoCA) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
MoCA is used to evaluate global cognition. Higher score indicates better performance.
Auditory Verbal Learning Test (AVLT) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
AVLT is used to evaluate verbal learning and memory ability. Higher score indicates better performance.
Digital span (DS) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
DS is used to assess attention. Higher score indicates better performance.
Verbal fluency test at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
Verbal fluency test is used to evaluate language function. Higher score indicates better performance.
Controlled Oral Word Association Test (COWAT) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
COWAT is used to evaluate language function. Higher score indicates better performance.
Stroop test at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
Stroop test is used to assess executive function. Higher score indicates better performance.
Activity of daily living (ADL) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
ADL is used to evaluate activities of daily living.
Brief Visuospatial Memory Test-Revised (BVMT-R) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
BVMT-R is used to evaluate spatial memory ability. Higher score indicates better performance.
Trail Making Test-A (TMT-A) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
TMT-A is used to assess information processing speed. Lower score indicates better performance.
Mini-Mental State Examination (MMSE) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
MMSE is used to evaluate global cognition. Higher score indicates better performance.
TMT-B at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
TMT-B is used to assess executive function. Lower score indicates better performance.
Benton Judgment of Line Orientation (JLO) at endpoint and change from baseline
时间窗: 48 weeks post-dose and change from baseline
JLO is used to assess visuospatial function. Higher score indicates better performance.
次要结局
- Global function at endpoint and change from baseline(48 weeks post-dose and change from baseline)
- Neuropsychiatric Inventory (NPI) at endpoint and change from baseline(48 weeks post-dose and change from baseline)
研究者
Nan Zhang, MD, PhD
Associate Professor
Tianjin Medical University General Hospital