This study is designed to evaluate the safety and efficacy of butylphthalide (NBP) in the treatment of cerebral small vessel disease through a multicenter, randomized,double-blind, placebo-controlled study. Butylphthalide Soft Capsule and placebo were prescribed to the experimental group and the control group for a period of 24-months, respectively. After that, the experimental group and the control group were given Butylphthalide Soft Capsule for 6 months.
Butylphthalide can protect mitochondrial function and inhibit neuronal apoptosis by significantly increasing the activity of mitochondrial ATP complex enzyme and mitochondrial respiratory chain complex enzyme IV, improving the fluidity of mitochondrial membrane and maintaining mitochondrial membrane potential. Butylphthalide can reconstruct microcirculation and protect mitochondria, which can protect neurovascular units in an all-round way. Findings from previous studies have shown that butylphthalide can improve the ability of daily living of patients with ischemic cerebrovascular disease and can enhance cognitive function of patients diagnosed as subcortical vascular cognitive impairment no dementia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
300
The experimental group will receive the Butylphthalide Soft Capsules during the 24-month intervention period. After the 24-month intervention,The experimental group will receive Butylphthalide Soft Capsules for the 6-month open treatment period.
The placebo group will receive the Placebo Soft Capsules during the 24-month intervention period. After the 24-month intervention,The placebo group will receive Butylphthalide Soft Capsules for the 6-month open treatment period.
Peking Union Medical College Hospital
Beijing, China
RECRUITINGThe occurrence of the composite endpoint
new stroke event (ischemic or haemorrhagic), new onset dementia, an increase of modified Rankin Score (mRS) by ≥2 points, severe disability (mRS≥5), or death
Time frame: 30 months
Change of CIBIC-Plus score
Through interviews with caregivers and patients, a brief assessment of the patient's mental state was made in terms of the patient's relevant history, physical appearance, psychological/cognitive status, behavior, and ability to live daily. According to the above, the patients were evaluated: 1) significant improvement, 2) improved vector, 3) slight improvement, 4) no change, 5) slight deterioration, 6) moderate deterioration, and 7) severe deterioration.
Time frame: 30 months
Change of ADAS-cog score
1. Recall common words 2. Name the 12 objects submitted and the fingers on the hand 3. Understand and complete 1-5 steps 4. Copy 4 geometric shapes 5. The ability to complete familiar but complex sequence activities 6. Evaluation of time and place orientation 7. Identify new words from words already given 8. Remember the instructions in the cognitive task 9. Evaluation of patients' ability to speak and communicate 10. Evaluation of patients' language ability 11. Ability to understand spoken language 12. Patient attention during measurement Scoring criteria for (1)-(7) :The score is incorrect number of steps. Scoring criteria for (8)-(12) : 0= none, 1= very light, 2= mild, 3= moderate, 4= moderate, 5= severe.
Time frame: 30 months
Volume changes of white matter hyperintensities observed on cerebral MRI
Nothing
Time frame: 30 months
The proportion of participants with an increase of mRS by≥ 2, or mRS≥5 for severe disability
Level 1: symptomatic, but not obviously disabled, able to complete daily work and activities Level 2: mildly disabled, unable to complete daily activities before illness, but able to take care of themselves Level 3: moderately disabled, needs some help, but cannot walk without help Level 4: moderate to severe disability, need help walking, need help to complete their own care Level 5: severely disabled, bedridden, incontinence, need daily care Level 6: death
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Time frame: 30 months
The proportion of participants with new onset dementia。New onset dementia meets the following three criteria:
1. Mini-Mental State Examination (MMSE) score\<20 (primary school) or \< 24 points (junior high school or above); MMSE is a scale assessing orientation, memory, attention, language, and visuospatial function. Scores in each item are combined to obtain a total score ranging from 0 to 30. Score of 24 or more indicates normal cognition 2. Clinical Dementia Rating-Sum of Boxes (CDR-SB)≥1 CDR assesses cognitive performance in six areas: memory, orientation, judgment \& problem solving, community affairs, home \& hobbies, and personal care. Scores in each of these are combined to obtain a composite score ranging from 0 to 3 3. Instrumental Activities of Daily Living (IADLs)\>26 points IADLs scale assesses 20 items of daily living ability. The score of each item ranges from 1 to 4 points: 1 is normal, and 4 indicate obvious functional decline. Scores in each item are combined to obtain a total score ranging from 20 to 80
Time frame: 30 months
The proportion of participants with death due to any known or unknown cause
The causes of death were classified as follows: ischemic stroke, hemorrhagic stroke, heart disease , hemorrhage (excluding intracranial hemorrhage), infection, malignant tumors, trauma, other vascular etiology (including pulmonary embolism), other non-vascular and unclear etiology.
Time frame: 30 months
Changes of the gait speed in three-meter walktest
Nothing
Time frame: 30 months
Changes in the number of silent brain infarcts
Nothing
Time frame: 30 months
Changes in the number of cerebral microbleeds
Nothing
Time frame: 30 months
Evolution of brain volumes (gray matter, white matter and CSF volumes)
Nothing
Time frame: 30 months