Clinical trial NCT02453932: Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
Official title: A Phase III, Multicenter, Randomized, Double-blind, Positive /Placebo Controlled, Parallel, Three Arms Study of Tianzhi Granule in Mild to Moderate Vascular Dementia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vascular Dementia
Keywords: Vascular dementia
Tianzhi granule
Herbal medicine
Randomized controlled trial
Three arms
Lead sponsor: Dongzhimen Hospital, Beijing
Sponsor class: OTHER
First posted: 2015-05-27
Enrollment: 543
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes of Vascular Dementia Assessment Scale-Cognitive Subscale(VADAS-cog) from baseline after 24 weeks' intervention
timeFrame: week 0, 4, 12, 24
measure: Changes of Clinician's Interview-Based Impression of Change-Plus carer Interview(CIBIC-plus) from baseline after 24 weeks' intervention
timeFrame: week 0, 4, 12, 24
Secondary outcomes:
measure: Changes of Mini-Mental State Examination(MMSE) from baseline after 24 weeks' treatment
timeFrame: week 0, 4, 12, 24
measure: Changes of Activity of Daily Living Scale(ADL) from baseline after 24 week's intervention
timeFrame: week 0, 4, 12, 24
measure: Changes of Clock Drawing Test(CDT) from baseline after 24 week's intervention
timeFrame: week 0, 4, 12, 24
measure: Changes of Trail Making Test (TMT) from baseline after 24 week's intervention
timeFrame: week 0, 4, 12, 24
measure: Changes of Neuropsychiatric Inventory(NPI) from baseline after 24 weeks' intervention
timeFrame: week 0, 4, 12, 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Dongzhimen Hospital,Beijing University of Chinese Medicine
state: Beijing
Study officials:
affiliation: Dongzhimen Hospital, Beijing
name: Jinzhou Tian, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shi J, Wei M, Ni J, Sun F, Sun L, Wang J, Yu T, Wang K, Lv P, Wang Y, Zhang Y, Gao X, Gao X, Luo B, Mao S, Zhang B, Ren X, Yu F, Hu W, Yin P, Wu N, Liu X, Bi Q, Wang Y, Tian J; CHASE Study Group. Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial. J Transl Med. 2020 Feb 13;18(1):76. doi: 10.1186/s12967-020-02232-z.