Efficacy and Safety of Qi Zhi Tong Luo Capsule in Vascular Cognitive Impairment: a Randomized, Double-blind, Placebo- Controlled, Multicentre Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 362
- 试验地点
- 1
- 主要终点
- Changes of Clinical Dementia Rating-Sum of the Boxes scale (CDR-SB) from baseline
研究概览
简要总结
Qi Zhi Tong Luo (QZTL) capsule, a traditional Chinese herbal medicine, which was used to treat stoke-related symptoms, include trouble speaking, paralysis and trouble walking. This study aimed to evaluate the efficacy and safety of QZTL capsule in the treatment of vascular cognitive impairment. This study was designed as randomized, double-blind, parallel, placebo-controlled, multicentre trial. It consisted of a single-blind run-in period using placebo only (2 weeks) and a double-blind treatment phase after randomization (24 weeks), and follow-up 12 weeks after withdrawal.The primary efficacy variables included changes from baseline in the Clinical Dementia Rating scale-Sum Box (CDR-SB) and the Mini-mental State Examination (MMSE) after 24 weeks of treatment. The secondary efficacy measurements include the Clock Drawing Test (CDT), Hopkins Verbal Learning Test (HVLT) and Ability of Daily Living (ADL).
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
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Decline in cognitive function from a prior baseline and impairment in at least 1 cognitive domain, the domain of cognition including executive function(Trail Making Test-part A(Chinese version,150s)>98s)), memory function decline (Hopkins verbal learning test free recall(36 points) <18.5 points), language function decline (Boston naming test (Chinese version 30 items)<22 points), and visuo-spatial functions (Clock drawing test(10 points)<8.5 points) ;
- •Evidence of cerebrovascular disease relies on structural magnetic resonance imaging (MRI) , history and clinical feature. The neuroimaging should include at least one of following: a) a single large vessel infarction which was sufficient to cause cognition decline; b) infarction at a single strategic place was sufficient to cause severe cognition decline( the thalamus, angular gyrus, and basal ganglia, including the caudate nucleus and globus pallidus); c) multiple lacunar infarctions (≥3) outside the brainstem, or 2 lacunar infarcts at key locations, a single lacunar focus with extensive white matter lesions(WMLs) ; d) extensive and integrated WMLs(Fazekas scale≥3 points) ; e) intracranial hemorrhage in key parts, or ≥2 intracranial hemorrhages; f) combination of above.
- •There was a clear temporal relationship between a vascular event and onset of cognitive deficit, cognitive impairment should appear within 3 months after a stroke, or abrupt deterioration, or stepwise progression of deficits; or cognitive impairment may be related to vascular factors, the Hachinski Ischemia scale (HIS) score ≥7;
- •And the patients must have adequate vision and hearing to participate in study assessments;
- •Have a stable caregiver;
- •Can read simple articles and write simple sentences;
- •Informed consent, signed informed consent by legal guardian.
排除标准
- •Evidence of other reasons caused cognitive impairment, like Alzheimer disease, frontotemporal dementia, Parkinson disease dementia, dementia with Lewy bodies, Huntington disease, etc;
- •Subdural hematoma, traffic hydrocephalus, brain tumor, thyroid disease, vitamin deficiency, or other diseases which can lead to cognitive impairment;
- •Major depression (Hamilton depression rating scale [HAMD] ≥17) or other mental disorders ;
- •History of drug or alcohol abuse in the past 6 month;
- •History of epilepsy;
- •Patients with myasthenia gravis;
- •Subject cannot complete related test due to severe neurologic deficits;
- •Other uncontrolled chronic illnesses, like severe cardiovascular disease (severe arrhythmia, myocardial infarction within 3 months, severe heart failure(New York Heart Association Functional Classification III and IV,); uncontrolled hypertension, diabetes);
- •Severe liver or kidney dysfunction (alanine aminotransferase or aspartate transaminase was more than 1.5 times the upper limit of normal, or serum creatinine was more than the upper limit of normal);
- •Concomitant use of the anticonvulsants, antipsychotics, cholinomimetic drugs, anticholinergic agents, anti-Parkinson drugs, cholinesterase inhibitors, memantine, nootropic drug, nimodipine, anticholinergic or anticholinergic antidepressant or anxiolytic and other cognition enhancers within 1 month;
- •Severe asthma and chronic obstructive pulmonary disease;
- •Patients with severe indigestion, gastrointestinal obstruction, gastric or duodenal ulcers;
- •Patients with glaucoma;
- •History of hypersensitivity to the treatment drugs;
- •Participate in other clinical study.
研究组 & 干预措施
Qi Zhi Tong Luo group
Patients were receiveed Qi Zhi Tong Luo Capsule 4 capsules, 2 times per day for 24 weeks. Each capsule was weighted 0.5g. Qi Zhi Tong Luo capsule (batch number: 20140805) were produced by Shanxi Zhendong Pharmaceutical Co., Ltd.
干预措施: Qi Zhi Tong Luo capsule (Drug)
Placebo group
Patients were allocated to placebo, 4 capsules, 2 times per day for 24 weeks. Placebo (batch number: 20140805) were produced by Shanxi Zhendong Pharmaceutical Co., Ltd.
干预措施: Placebos (Drug)
结局指标
主要结局
Changes of Clinical Dementia Rating-Sum of the Boxes scale (CDR-SB) from baseline
时间窗: week 0, 12, 24,36
CDR-SB is a standard for disease grading in clinical studies of dementia and is used for overall endpoint assessment in clinical trials. The CDR-SB scores from 0-18 points, and a higher score indicates higher impairment.
Changes of Mini-mental State Examination(MMSE from baseline
时间窗: week 0, 12, 24,36
MMSE, 0-30 points, a lower score means severe global cognition impairment, which is used for overall endpoint assessment in clinical trials.
次要结局
- Changes of Hopkins Verbal Learning Test from baseline(week 0, 12, 24,36)
- Changes of Clock drawing test from baseline(week 0, 12, 24,36)
- Changes of Ability of daily living scale from baseline(week 0, 12, 24,36)
研究者
Jinzhou Tian
Vice president
Dongzhimen Hospital, Beijing