Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia

Study Overview
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Brief Summary
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The study will be a 24-week multicentre, double-blind, placebo-controlled phase Ⅱa trial with 4 treatment arms in China. Participants aged 55-80 years will be randomized to TMBCZG-high dose(84mg per day), TMBCZG- medium dose(56mg per day), TMBCZG- low dose(28mg per day) or to placebo. The primary endpoint will be VADAS-Cog and CDR-SB. Secondary outcomes included changes in MMSE and ADL. Patients' safety will be assessed by recording of adverse events, clinical examinations, electrocardiography and laboratory tests. The patients, caregivers, and investigators will be blinded to the treatment allocations.

Official Title
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Efficacy and Safety of Twice Daily TMBCZG in Mild to Moderate Vascular Dementia: Randomized, Double Blind, Parallel Group, Placebo Controlled, Multicenter Trial

Conditions
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Vascular Dementia

Intervention / Treatment
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* Drug: TMBCZG
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients meeting the clinical diagnosis of probable vascular dementia(VaD) established according to 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: Dementia defined by clinical core criteria, Cerebrovascular disease, defined by history of stroke, as well as multiple basal ganglia and white matter lacunes, or extensive periventricular white matter lesions( excluded medial temporal lobe atrophy or other special image), A relationship between dementia and Cerebrovascular disease, manifested or inferred by the presence of one or more of the following: (a) onset of dementia within 3 months following a recognized stroke; (b) abrupt deterioration in cognitive functions; or fluctuating, stepwise progression of cognitive deficits. Mild to Moderate Dementia with MMSE score of ≤26 and ≥11; Aged ≥55 and ≤80 years old in both gender; Weighing of ≥45kg and ≤90kg; Adequate vision and hearing ability to complete all study tests; With a stable caregiver. Have a certain level of language competence (can read simple articles and write simple sentences); Informed consent, signed informed consent by legal guardian. Exclusion Criteria: A medical history of other dementia types, like mixed dementia, Alzheimer's disease, frontotemporal dementia, Parkinson's disease dementia, dementia with Lewy bodies, Huntington disease, et al; Subdural hematoma, traffic hydrocephalus, brain tumor, thyroid disease,vitamin deficiency or other diseases which can lead to cognitive impediment; Major depression (HAMD≥17) or major anxious(HAMA≥12); Subject can't complete related test due to severe neurologic deficits, such as hemiplegia, aphasia, audio-visual disorder and so forth; Severe cardiovascular disease(severe arrhythmia, myocardial infarction within 3 months, New York Heart Association Functional Classification III-IV, systolic pressure≥180mmHg or ≤90mmHg); Severe liver or kidney dysfunction (alanine aminotransferase or aspartate transaminase is more than 1.5 times the upper limit of normal, or serum creatinine is more than the upper limit of normal); Uncontrolled diabetes(glycosylated hemoglobin is more than 2 times the upper limit of normal); Asthma, chronic obstructive pulmonary disease, multiple neuritis, myasthenia gravis and muscle atrophy; Severe indigestion, gastrointestinal obstruction, gastric and duodenal ulcers and other gastrointestinal disorders that can affect drug absorption; A medical history of epileptic history, glaucoma, alcoholism, or psycho-substance abuse; Subject has been taking cholinesterase inhibitors, memantine, nimodipine or herbal medicine with function of improving cognition in the past one month; Use of sympathomimetic or antihistamines drugs within 48h before assessment; Allergic constitution or allergic reactions to experimental drug; According to the assessment of the investigator, subject cann't complete the study due to poor compliance or other reasons; Subject is participating in other clinical trials or participated in the past 1 month.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo identified to TMBCZG,0.1g per pill which contains 0mg TMBCZG，3 pills per time, 2 times per day for 24 weeks. | Other: placebo<br>* 0.1g per pill which contains 0mg TMBCZG<br>|
| Experimental: TMBCZG-high dose<br>TMBCZG, 0.1g per pill which contains 14mg TMBCZG, 3 pills per time, 2 times per day for 24 weeks. | Drug: TMBCZG<br>* 0.1g per pill which contains 14mg TMBCZG<br>* Other names: TianMaYouJiDuoSuanBianZhiGanPian(TMYJDSBZG);|
| Experimental: TMBCZG-medium dose<br>TMBCZG( 0.1g per pill which contains 14mg TMBCZG) and placebo identified to TMBCZG(0.1g per pill which contains 0mg TMBCZG), 2 TMBCZG pills and 1 placebo pill per time, 2 times per day for 24 weeks. | Drug: TMBCZG<br>* 0.1g per pill which contains 14mg TMBCZG<br>* Other names: TianMaYouJiDuoSuanBianZhiGanPian(TMYJDSBZG);Other: placebo<br>* 0.1g per pill which contains 0mg TMBCZG<br>|
| Experimental: TMBCZG-low dose<br>TMBCZG( 0.1g per pill which contains 14mg TMBCZG) and placebo identified to TMBCZG(0.1g per pill which contains 0mg TMBCZG), 1 TMBCZG pills and 2 placebo pill per time, 2 times per day for 24 weeks. | Drug: TMBCZG<br>* 0.1g per pill which contains 14mg TMBCZG<br>* Other names: TianMaYouJiDuoSuanBianZhiGanPian(TMYJDSBZG);Other: placebo<br>* 0.1g per pill which contains 0mg TMBCZG<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Dementia Assessment Scale-cognitive subscale(VADAS-Cog) | Change from baseline to end of double-blind treatment of VADAS-Cog. | baseline, 4-week, 12-week, 24-week and 28-week. | 
| Clinical Dementia Rating-Sum of Boxes (CDR-SB) | Change from baseline to end of double-blind treatment of CDR-SB. | baseline, 4-week, 12-week, 24-week and 28-week. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-Mental State Examination (MMSE) | Change from baseline to end of double-blind treatment of MMSE. | baseline, 4-week, 12-week, 24-week and 28-week. | 
| Activities of daily living (ADL) | Change from baseline to end of double-blind treatment of ADL. | baseline, 4-week, 12-week, 24-week and 28-week. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herbal therapy, Randomized controlled trial, Vascular Dementia