CerebrAlcare Pills on CereBral Small VesseL DiseasE（CABLE）：A Randomized, Double-blinded, Placebo-controlled, Multi-center Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Progression in cognition function
研究概览
简要总结
This is a randomized, double-blinded, placebo-controlled, multicenter trial. Cerebral small vessel disease (CSVD) patients will be diagnosed by Magnetic Resonance Imaging (MRI) and randomized into treatment or control groups. The purpose of this trial is to assess the efficacy of cerebralcare pills on cerebral small vessel disease.
详细描述
Cerebral small vessel disease (CSVD) is prevalent in the aging population with insidious onset, almost affecting all levels of the brain vasculature, and challenges the social and healthcare system worldwide. CSVD is the major cause of 25% of strokes and more than doubles the odds of recurrent stroke; furthermore, it contributes to 45% of dementia cases and to global functional decline. However, an incomplete understanding of the pathogenesis of CSVD limits prevention and treatment efforts.
Cerebralcare Granule (CG) or Yangxue Qingnao granule, is a polyherbal medicine that was approved in 1997 by the China State Food and Drug Administration for the treatment of headaches and dizziness associated with cerebrovascular diseases. Cerebralcare pill is composed of 11 herbs. These herbs contain small molecules with various pharmacological actions. Cerebralcare pills have the same component as CG. Previous studies have demonstrated that CG significantly attenuated ischemia-reperfusion induced dysfunction, structural abnormalities in the microcirculation, and inflammatory injury. There are also studies confirming that CG also improved cognition function, improved cerebral microcirculation disorders, and hemodynamics.
Patients enrolled will be randomly assigned to either the treatment or control group to receive Brain Pill/Brain Pill placebo (from randomization to 6 months at a dose of 2 packs per day). Face-to-face interviews will be conducted at baseline, day 90, day 180, and 1 year after randomization.
The primary endpoint is the progression in cognition function which is assessed by Montreal Cognitive Assessment (MoCA) score. The secondary endpoints include changes in clinical characters, imaging markers (number and volume of white matter, number of lacunes, microbleeds, enlarged perivascular space ), hemodynamic parameters, Chinese medical symptoms, blood-brain barrier (BBB) permeability, proteomics, and inflammatory markers. The safety endpoints include severe hemorrhage events, symptomatic and asymptomatic intracranial hemorrhage, moderate hemorrhage, overall mortality, and serious adverse events.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •45-75 years old;
- •No gender limitation;
- •Cerebral small vessel disease is observed on brain MRI. White matter hyperintensity, Fazekas score ≥ 1 and combined more than 2 vascular risk factors (hypertension, hyperlipidemia, diabetes, obesity, smoking, and other vascular events except stroke) or combined with lacunar focus or Imaging findings suggest new subcortical lacunar infarction (within 7 days).
- •Mild or moderate vascular cognitive impairment(16 ≤ MoCA ≤ 24 score, for patients with primary school degree or below,15 ≤ MoCA ≤ 23 score).
- •Daily life independence (mRS ≤ 2).
- •Sign informed consent.
- •The imaging definition of small vessel disease refers to the strong guideline The total score of Fazekas was 6, which was the sum of Fazekas scores of subcortical and periventricular white matter lesions.
- •New subcortical lacunar infarction: head MRI examination, subcortical, basal ganglia or brain stem DWI showed high signal (ADC diffusion limited) lesions with diameter < 20 mm, with or without corresponding clinical symptoms; There were new clinical symptoms. FLAIR sequence of head MRI showed flair hyperintense lesions (diameter < 20 mm) in subcortical, basal ganglia or pons.
排除标准
- •Cerebral hemorrhage and subarachnoid hemorrhage occurred within 30 days.
- •Symptomatic middle cerebral artery and/or internal carotid artery stenosis, stenosis rate ≥ 50%; asymptomatic middle cerebral artery and/or internal carotid artery stenosis, stenosis rate ≥ 70%.
- •Coronary CTA or coronary angiography showed severe three vessel lesions or frequent angina pectoris within 30 days.
- •Chronic kidney disease stage 4 or
- •Resistant hypertension which could not be controlled by medicine (SBP > 180mmHg or DBP > 110mmHg).
- •Resistant hyperglycemia which could not be controlled by medicine（fasting blood glucose > 10mmol/L or HB1AC > 7%).
- •In acute cerebral infarction, the lesions showed high signal intensity on DWI, and the diameter was more than 20 mm or history of assive cerebral infarction within 30 days.
- •Neurodegenerative diseases, such as AD and PD, have been diagnosed.
- •There are clear non angiogenic white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy diseases, etc.
- •Untreated cerebrovascular malformations or intracranial aneurysms (d > 3mm).
- •Active gastrointestinal bleeding.
- •Coagulation dysfunction or history of systemic bleeding.
- •Hemorrhagic tendency (including but not limited to)：PLT<100×109/L; heparin treatment within 48h; APTT ≥ 35s; current use of warfarin, INR > 1.7; current use of novel oral anticoagulants; current use of direct thrombin or factor Xa inhibitor.
- •Severe hepatic or renal or heat insufficiency before randomization (severe hepatic insufficiency refers to ALT or AST > 2 times the upper limit of normal; severe renal insufficiency refers to serum creatinine> 1.5 times the upper limit of normal or eGFR<40 ml/min/1.73m2; severe heat insufficiency refers to NYHA stage 3 and 4).
- •History of intracranial or intramedullary surgery within three months of randomization.
- •The patient has used or is using chinese medicine with similar components to CerebrAlcare pill/granule (including Tianshu capsule, Toutongning capsule, Naoxintong capsule, Danzhen Toutou capsule, Yindanxinnaotong soft capsule, Naoxinqing Tablet, Bazhen pill and Shiquandabu pill) within 14 days.
- •Definite indications for anticoagulation (suspicion of cardioembolism, e.g. atrial fibrillation, known heart valve prosthesis, atrial myxoma, endocarditis, etc.) or definite indications for dual antiplatelet therapy (e.g. recent coronary or cerebral artery stent implantation).
- •Other surgical or interventional therapy planned within 1 year requiring experimental drugs discontinuation.
- •Childbearing-age women who do not take effective methods of contraception without negative records of pregnancy tests.
- •Known to be allergic to CerebrAlcare pill/granule.
- •Contraindications of MRI examination (such as claustrophobia).
- •With severe organic diseases, such as malignant tumor, the expected survival time is less than 1 years.
- •Due to geographical or other reasons can not cooperate to complete the follow-up.
- •Patients also participated in other clinical trials.
研究组 & 干预措施
Cerebralcare pills placebo group
This group will receive Cerebralcare pills placebo, 2 packages, twice a day, from the day of randomization to 6 months.
干预措施: Cerebralcare pills placebo (Drug)
Cerebralcare pills group
This group will receive Cerebralcare pills, 2 packages, twice a day, from the day of randomization to 6 months.
干预措施: Cerebralcare pills (Drug)
结局指标
主要结局
Progression in cognition function
时间窗: 6 months after randomization
Cognition function assessed by Montreal Cognitive Assessment (MoCA) score. Score range 0-30. Higher scores mean a better outcome..
次要结局
- Changes in both systolic and diastolic blood pressure(3 months, 6 months and 1 year after randomization)
- EuroQol five dimensions questionnaire (EQ-5D)(3 months, 6 months and 1 year after randomization)
- Changes of white matter hyperintensities(WMHs) volume(6 months and 1 year after randomization)
- Number of lacunes(6 months and 1 year after randomization)
- Composite vascular events(3 months, 6 months and 1 year after randomization)
- Rey auditory verbal learning test（RAVLT）(3 months, 6 months and 1 year after randomization)
- Headache impact test 6(HIT-6）(3 months, 6 months and 1 year after randomization)
- Number of cerebral microbleeds(6 months and 1 year after randomization)
- Moderate and/or severe hemorrhage events(3 months, 6 months and 1 year after randomization)
- Generalized Anxiety Disorder 7（GAD-7)(3 months, 6 months and 1 year after randomization)
- Changes in hemodynamic parameters(6 months and 1 year after randomization)
- changes in Chinese medical symptoms(6 months and 1 year after randomization)
- Difference of recurrent stroke between groups(3 months, 6 months and 1 year after randomization)
- changes in Blood-Brain Barrier (BBB) Permeability between groups(6 months and 1 year after randomization)
- Compare protein profiles observed among different groups.(6 months and 1 year after randomization)
- Adverse events and severe adverse events(3 months, 6 months and 1 year after randomization)
- Self-rating depression scale(3 months, 6 months and 1 year after randomization)
- Dizziness handicap inventory（DHI）(3 months, 6 months and 1 year after randomization)
- All-cause death(3 months, 6 months and 1 year after randomization)
- Stroop Color Word Test(3 months, 6 months and 1 year after randomization)
- Severity of white matter hyperintensities(WMHs)(6 months and 1 year after randomization)
- Number of enlarged perivascular space(6 months and 1 year after randomization)
- Symptomatic and/or asymptomatic intracranial hemorrhage(3 months, 6 months and 1 year after randomization)
研究者
yilong Wang
Vice President of Beijing Tiantan Hospital
Beijing Tiantan Hospital