Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia

A Phase III, Multicenter, Randomized, Double-blind, Positive /Placebo Controlled, Parallel, Three Arms Study of Tianzhi Granule in Mild to Moderate Vascular Dementia

This ongoing study aimed to evaluate the efficacy and safety of Tianzhi granule in mild to moderate vascular dementia in a more reasonable design.

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

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.