A Phase III, Multicenter, Randomized, Double-blind, Positive /Placebo Controlled, Parallel, Three Arms Study of Tianzhi Granule in Mild to Moderate Vascular Dementia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 543
- 试验地点
- 1
- 主要终点
- Changes of Clinician's Interview-Based Impression of Change-Plus carer Interview(CIBIC-plus) from baseline after 24 weeks' intervention
研究概览
简要总结
This ongoing study aimed to evaluate the efficacy and safety of Tianzhi granule in mild to moderate vascular dementia in a more reasonable design.
详细描述
This study is a 24-weeks, multicenter, randomized, double-blind, double- placebo, parallel controlled phase III trial being carried out in 23 centers around China. The study population includes mild to moderate VaD patients (planned a total of 630) aged 45-85 in both gender. Participants will be randomly allocated to TZK (15g/d) and placebo identified to donepezil, donepezil (5mg/d) and placebo identified to TZK, or placebo identified to TZK and placebo identified to donepezil for a 24-weeks double-blind treatment period . The primary outcome measure is change from baseline in the Vascular Dementia Assessment Scale-Cognitive Subscale and Clinician's Interview-Based Impression of Change-Plus carer Interview. The secondary outcomes are changes from baseline in the Mini-Mental State Examination, Activity of Daily Living Scale, Clock Drawing Test, Trail Making Test and Neuropsychiatric Inventory. Safety is being assessed by observing side effects and adverse reaction during the entire treatment period. Statistical analysis will be conducted according to per-protocol population and intend-to-treat population and the safety will be analyzed in safety set.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inpatients and outpatients meeting the diagnostic criteria probable VaD established according to the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) （DSM-Ⅳ） and the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN)were eligible to participate,
- •diagnosis of mild to moderate vascular dementia;
- •Chinese-speaking patients aged ≥45 and≤85 years old in both gender;
- •weighing between 45 and 90kg;
- •fully conscious;
- •MMSE score of≤26 and ≥14;
- •HIS score of ≥7;
- •adequate vision and hearing ability to complete all study tests;
- •with a stable caregiver.
排除标准
- •Patients will be excluded from the enrollment if they meet any of the followings:
- •a medical history of other dementia types, like Alzheimer's disease, Parkinson's disease dementia, Huntington disease, Normal pressure hydrocephalus, et al;
- •major depression (HAMD for 17 items>17) or psychotic disorder;
- •acute stage of cerebral hemorrhage or subarachnoid hemorrhage;
- •hypothyroidism;
- •drug or alcohol abuse;
- •epilepsy history; myasthenia gravis history;
- •severe cardiovascular disease(severe arrhythmia with heart rate≥100 or≤60 times per min, left bundle branch block, myocardial infarction within 3 months, systolic pressure≥180mmHg or ≤90mmHg);
- •severe liver or kidney dysfunction (alanine aminotransferase>60 IU/L, aspartate transaminase>60 IU/L or serum creatinine >266μmol/L);
- •severe asthma or chronic obstructive pulmonary disease;
- •gastrointestinal tract obstruction or severe peptic ulcer; glaucoma;
- •administration of cholinesterase inhibitors, memantine or nimodipine in the last month;
- •use of sympathomimetic agent, antihistamine drug, antianxiety drugs or tranquilizer within 48h before assessment;
- •use of antipsychotic drugs within 72h before assessment;
- •participation in other clinical trials; allergic history to any type of medication used in this study.
研究组 & 干预措施
Tianzhi granule
Tianzhi granule and placebo identified to donepezil
干预措施: Tianzhi granule and placebo identified to donepezil (Drug)
Donepezil
Donepezil and placebo identified to Tianzhi granule
干预措施: Donepezil and placebo identified to Tianzhi granule (Drug)
Placebo
Placebo identified toTianzhi granule and placebo identified to donepezil
干预措施: Placebo (Drug)
结局指标
主要结局
Changes of Clinician's Interview-Based Impression of Change-Plus carer Interview(CIBIC-plus) from baseline after 24 weeks' intervention
时间窗: week 0, 4, 12, 24
Overall clinical response: CIBIC-plus is a 7-point scale which provides an index of clinically important change for dementia patients. It is a global measure of detectable change in concentration, orientation, memory, language, behavior, initiative and activities of daily living, usually requiring separate interviews with patients and caregivers,the CIBIC-plus will be conducted at baseline, 4weeks, 12weeks, 24weeks
Changes of Vascular Dementia Assessment Scale-Cognitive Subscale(VADAS-cog) from baseline after 24 weeks' intervention
时间窗: week 0, 4, 12, 24
Cognition : VaDAS-cog is a revision of the ADAS-cog to be a better measure in vascular conditions. The original ADAS-cog developed by Rosen et al., measures cognitive performance by combining ratings of 11 items. The cognitive domains mainly addressed by ADAS-cog are memory (short term), language, ability to orientate (reflects memory), construction/planning of simple designs and performance. In addition to ADAS-cog, the VaDAS-cog comprises additional frontal lobe tests reflecting attention, working memory, executive function, and verbal fluency.The VADAS-cog will conducted at baseline, 4weeks, 12weeks, 24weeks
次要结局
- Changes of Trail Making Test (TMT) from baseline after 24 week's intervention(week 0, 4, 12, 24)
- Changes of Neuropsychiatric Inventory(NPI) from baseline after 24 weeks' intervention(week 0, 4, 12, 24)
- Changes of Mini-Mental State Examination(MMSE) from baseline after 24 weeks' treatment(week 0, 4, 12, 24)
- Changes of Activity of Daily Living Scale(ADL) from baseline after 24 week's intervention(week 0, 4, 12, 24)
- Changes of Clock Drawing Test(CDT) from baseline after 24 week's intervention(week 0, 4, 12, 24)
研究者
Jinzhou Tian
MD，PhD
Dongzhimen Hospital, Beijing