Butylphthalide soft capsule has been confirmed to have beneficial effects for patients with vascular dementia (VaD) in clinical trial of phase II study. So the investigators hypothesize that Butylphthalide soft capsule may have same beneficial effects for patients with VaD in an extended samples in phase III study. In present study the investigators will recruit patients with mild to moderate VaD in a multi-center, random, double blind and placebo control methods to confirm the efficacy and safety of Butylphthalide soft capsule. The outcome measures include general cognitive function, executive function, daily living skills, and mental behavior changes of symptoms in VaD patients.
Butylphthalide soft capsule is a synthetic chiral compound containing L- and D-isomers of butylphthalide. Studies in the past several decades have demonstrated that it could alleviate the learning and memory deficits induced by cerebral ischemia in rats. The phase II study enrolled 281 patients showed greater effects than placebo on ADAS-cog and CIBIC-plus. Butylphthalide soft capsule were uncommon and primarily consisted of mild gastrointestinal symptoms. In the present phase III study the investigators will re-assess the efficacy and the safety of Butylphthalide soft capsule for the treatment of mild to moderate vascular dementia in 700 subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
707
700 subjects are randomly divided into two groups by 1:1. About 350 patients in the active group take two pills(100mg each) of Butylphthalide soft capsule each time, three times a day, 0.5 hours before meal, taking with lukewarm water.
700 subjects are randomly divided into two groups by 1:1. About 350 patients in the active group take two pills of placebo soft capsule each time, three times a day, 0.5 hours before meal, taking with lukewarm water.
Xuanwu Hospital of Capital Medical University
Beijing, Beijing Municipality, China
Vascular Dementia Assessment Scale-cognitive Subscale(VaDAS-cog)
The group difference between the treatment group and the control group in the difference between the Vascular AD Assessment Scale Cognitive Subscale (VaDAS-cog) score at weeks 13, 26, 39 and 52 and the baseline score. The 6 areas of the cognitive function assessed by VaDAS-cog include the memory, the language competence, the orientation, the inferential capability, the practical ability and the comprehension. The total score is from 0 to 90 and the lower the score the milder the disease.
Time frame: Change from baseline VaDAS-cog score at Week 52
Clinician Interview Based Impression of Severity (CIBIC-plus)
The group difference between the treatment group and the control group in the difference between the Clinician Interview Based Impression of Severity (CIBIC-plus) score at weeks 13, 26, 39 and 52 and the baseline score. CIBIC-plus is a kind of scale that is assessed based on the clinical changes of the patient according to the impression obtained through interviewing the patient and other insiders. The score is from 1 to 7. And 1 indicates that the recovery is optimal, 4 indicates that there is no change and 7 indicates overall worsening.
Time frame: Change from baseline CIBIC-plus score at Week 52
Alzheimer's Disease Co-operative Study Activities of Daily Living (ADCS-ADL)
The group difference in the difference between the Alzheimer's Disease Co-operative Study Activities of Daily Living (ADCS-ADL) scores at weeks 13 (±7 days), week 26 (±7 days) , week 39 (±7 days) and week 52 (±7 days) and the base line score.
Time frame: Change from baseline ADCS-ADL score at Week 52
Neuropsychiatric Inventory (NPI)
It evaluates both the presence and severity of 12 neuropsychiatric features. The caregiver is asked to rate the frequency of the symptoms of that domain on a scale of 1 to 4 (1 = occasionally, less than once per week; 4 = very frequently, once or more per day or continuously) as well as their severity (1 = mild, 2 = moderate, 3 = severe). The total score for each domain is calculated by multiplying the frequency by the severity. A total score is calculated by adding all the domain scores together. Caregiver distress is rated by the caregiver on a six-point scale from 0 (no distress) to 5 (very severe or extreme distress). The total score of the caregiver's distress is obtained separately. The total NPI score is from 0 to 144 and the lower the score the milder the disease, the total caregiver distress score is from 0 to 6. The group difference between the NPI scores at weeks 13 (±7 days), week 26 (±7 days), week 39 (±7 days) and week 52 (±7 days) and the base line score.
Time frame: Change from baseline NPI score at Week 52
Mini-mental State Examination (MMSE)
The group difference in the difference between the Mini-mental State Examination (MMSE) scores at weeks 13 (±7 days), week 26 (±7 days), week 39 (±7 days) and week 52 (±7 days) and the baseline score.
Time frame: Change from baseline MMSE score at Week 52
MRI
The changes before and after the treatment at the cranial MRI bilateral hippocampus, the gyrus cinguli, the posterior horn of lateral ventricle, the infarction and the frontal temporal lobe white matter volume before the treatment, and at weeks 26 (± 7days) and 52 (±7days).
Time frame: Change from baseline MRI at Week 52
Blood biomarker
The concentration of BDNF and VEGF measured before the treatment, and at weeks 26 (± 7days) and 52 (±7 days) respectively.
Time frame: Change from baseline concentration of BDNF and VEGF at Week 52
MI/Cr ratio
The myoinositol (MI) and the creatine (Cr) levels (obtain the MI/Cr ratio) measured before the treatment, and at weeks 26 and 52 respectively.
Time frame: Change from baseline MI/Cr ratio at Week 52
Acetyl choline level
The concentration of acetyl choline in the blood measured before the treatment, and at weeks 26 (± 7days) and 52 (± 7days) respectively.
Time frame: Change from baseline concentration of acetyl choline at Week 52
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