Cerebral Small Vessel DiseasesMAP-CSVDNCT04078204
A Clinical Study on the Treatment of Cerebral Small Vascular Disease
A study testing Butylphthalide Soft Capsules in people with Cerebral Small Vessel Diseases, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Cerebral Small Vessel Diseases
- What is being tested?
- Butylphthalide Soft Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 25 Apr 2018to Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 50-80 years of age;
- all subjects with a culture level of primary school or above;
- Cerebral MRI demonstrated that patients with white matter hyperintense signal of vascular origin (Fazekas score≥ 2 points) and lacunar lesions (≥ 2);
- Consistent with at least one of the following clinical manifestations: (1)Subjects with a history of lacunar stroke syndrome more than 6-months before study initiation(Patients should have one of the traditional clinical lacunar syndromes and a new symptomatic lesion with a diameter of less than 20mm observed in subcortical white matter or basal ganglia), without a stenosis of greater than 50% in ipsilateral internal carotid artery or middle cerebral artery.) (2)Subjects with cognitive impairment (impairment involving memory and/or other cognitive domains and lasting for at least 3-months) have at least one domain rating of CDR > 0.5. Cognitive impairment and cerebrovascular disease are likely to have a causal relationship, showing sudden or fluctuating cognitive decline with ladder-like progress.
- Modified Rankin score ≤ 3 points; MMSE ≥ 10 points;
- Subjects have stable and reliable caregivers who must be able to communicate frequently with the subjects (at least 4 days a week, at least 2 hours a day). The caregivers will help the subjects participate in the whole process of the study. The caregiver must accompany the subjects to participate in the research visits, and must fully interact and communicate with the subjects in order to provide valuable information for CIBIC-plus, ADL, NPI and other scales.
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- Female patients are menopausal women (menopause ≥ 24 weeks), or have undergone surgical sterilization or have agreed to take effective contraceptive measures during the trial period.
- If patients use antipsychotic drugs (risperidone, quetiapine or olanzapine), anti-anxiety and depression drugs, sedative and hypnotic drugs and other drugs before screening, they need to take them stably for at least one month before screening, and try to maintain the dose stability during the research process. Sedative and hypnotic drugs such as zopiclone, alprazolam and estazolam may be used when necessary, but they should not be used within 8 hours of visiting time.
- Consent to participation in this study with the written informed consents obtained from all patients or their legal surrogates.
Who cannot join
- New onset cerebral infarction or intracranial hemorrhage within 6 months;
- Complicated with cerebral cortical infarction or cerebral hemorrhage,hydrocephalus and other white matter lesions of non-vascular origin (multiple sclerosis, carbon monoxide poisoning encephalopathy, etc.);
- Systemic diseases that may be responsible for cognitive impairment (such as liver and kidney dysfunction, endocrine diseases, vitamin deficiency, systemic autoimmune diseases, etc.);
- Depression and depression related conditions (Hamilton Depression Scale score ≥ 17 points), or other unrelated serious mental disorders (schizophrenia, bipolar affective disorder or delirium) or serious neurological diseases (such as central nervous system infection (for example AIDS, syphilis), Creutzfeldt-Jakob disease, Huntington's chorea and primary Parkinson's disease,Lewy body dementia,corticobasal ganglia degeneration, brain trauma, epilepsy, brain tumors (with an exception of patients with meningioma which could not attribute to cognitive impairment based on the judgement of the researchers.)
- Those who use other drugs that affect the safety or efficacy evaluation of the tested drugs and disagree with withdrawal, such as NBP,cholinesterase inhibitors (Arizona, Essene, Galantamine, Huperzine A Tablets, Benzhexol Hydrochloride etc.), N-methyl-D-aspartic acid (NMDA) antagonists (such as Memantine, Amantadine, Ketamine, etc.);
- Patients allergic or intolerant to butylphthalide (NBP) ;
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- Patients with severe cardiac,pulmonary and renal insufficiency (creatinine > 2.0 mg/dl or 178umol/L), severe liver dysfunction (ALT or AST >3 times of upper limit of the normal value), any malignancies and those with a life expectancy less than 2 years;
- Patients with Coagulation dysfunction or thrombocytopenia (platelet < 100 *10^9/L);
- Contraindication for MR examination.
- Women during pregnancy and lactation period or plan to be pregnant.
- Patients who are participating in other interventional clinical studies or have participated in other interventional clinical studies in the past three months;
- Patients who could not be followed up as required during the study period;
- Patients unable to complete neuropsychological evaluations due to illiteracy or irreparable audiovisual impairment;
- Refractory hypertension: blood pressure ≥180/110 mmHg;
- The subjects are the investigators and immediate family members participating in the study, employees and immediate family members of embip.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing
About this study
Official title: A Multi-center, Randomized, Double-Blind, Placebo-Controlled Study of Dl-3-Butylphthalide on the Treatment of Small Cerebral Vessel Disease
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.
Read the detailed description
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.
- Conditions
- Cerebral Small Vessel Diseases
- Being tested
- Butylphthalide Soft Capsules, placebo Soft Capsules
- Keywords
- Butylphthalide, Cerebral Small Vessel Diseases, Clinical Study
- Medical subject headings
- Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Butylphthalide Soft CapsulesDrug
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.
placebo Soft CapsulesDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Butylphthalide Soft Capsules | Experimental | Two Butylphthalide soft capsules will be taken three times a day before meals. Receives: Drug: Butylphthalide Soft Capsules |
| Placebo Soft Capsules | Placebo comparator | Two placebo soft capsules will be taken three times a day before meals. Receives: Drug: placebo Soft Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
The 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
Measured: 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.
Measured: 30 months
Change of ADAS-cog score
- Recall common words
- Name the 12 objects submitted and the fingers on the hand
- Understand and complete 1-5 steps
- Copy 4 geometric shapes
- The ability to complete familiar but complex sequence activities
- Evaluation of time and place orientation
- Identify new words from words already given
- Remember the instructions in the cognitive task
- Evaluation of patients' ability to speak and communicate
- Evaluation of patients' language ability
- Ability to understand spoken language
- 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.
Measured: 30 months
Volume changes of white matter hyperintensities observed on cerebral MRI
Nothing
Measured: 30 months
Secondary outcomes (7)
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
Measured: 30 months
The proportion of participants with new onset dementia。New onset dementia meets the following three criteria:
- 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
- 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
- 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
Measured: 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.
Measured: 30 months
Changes of the gait speed in three-meter walktest
Nothing
Measured: 30 months
Changes in the number of silent brain infarcts
Nothing
Measured: 30 months
Changes in the number of cerebral microbleeds
Nothing
Measured: 30 months
Evolution of brain volumes (gray matter, white matter and CSF volumes)
Nothing
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start25 Apr 2018
- Primary completionFeb 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Small Vessel DiseasesStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04078204
- Sponsor's protocol ID
- 2018ZX09711001-003-021
- Acronym
- MAP-CSVD
- Status last verified
- Sep 2019
- First submitted
- 24 Feb 2019
- Last updated
- 4 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-Blind, Placebo-Controlled Study of Dl-3-Butylphthalide on the Treatment of Small Cerebral Vessel Disease
- ClinicalTrials.gov ID
- NCT04078204
- Acronym / sponsor ID
- MAP-CSVD / 2018ZX09711001-003-021
- Conditions
- Cerebral Small Vessel Diseases
- Keywords
- Butylphthalide, Cerebral Small Vessel Diseases, Clinical Study
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 25 Apr 2018 (actual)
- Primary completion
- Feb 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 4 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Butylphthalide Soft Capsules | Experimental | Drug: Butylphthalide Soft CapsulesTwo Butylphthalide soft capsules will be taken three times a day before meals. |
| Placebo Soft Capsules | Placebo comparator | Drug: placebo Soft CapsulesTwo placebo soft capsules will be taken three times a day before meals. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 50-80 years of age;
- all subjects with a culture level of primary school or above;
- Cerebral MRI demonstrated that patients with white matter hyperintense signal of vascular origin (Fazekas score≥ 2 points) and lacunar lesions (≥ 2);
- Consistent with at least one of the following clinical manifestations: (1)Subjects with a history of lacunar stroke syndrome more than 6-months before study initiation(Patients should have one of the traditional clinical lacunar syndromes and a new symptomatic lesion with a diameter of less than 20mm observed in subcortical white matter or basal ganglia), without a stenosis of greater than 50% in ipsilateral internal carotid artery or middle cerebral artery.) (2)Subjects with cognitive impairment (impairment involving memory and/or other cognitive domains and lasting for at least 3-months) have at least one domain rating of CDR > 0.5. Cognitive impairment and cerebrovascular disease are likely to have a causal relationship, showing sudden or fluctuating cognitive decline with ladder-like progress.
- Modified Rankin score ≤ 3 points; MMSE ≥ 10 points;
Key exclusion criteria (15 listed)
- New onset cerebral infarction or intracranial hemorrhage within 6 months;
- Complicated with cerebral cortical infarction or cerebral hemorrhage,hydrocephalus and other white matter lesions of non-vascular origin (multiple sclerosis, carbon monoxide poisoning encephalopathy, etc.);
- Systemic diseases that may be responsible for cognitive impairment (such as liver and kidney dysfunction, endocrine diseases, vitamin deficiency, systemic autoimmune diseases, etc.);
- Depression and depression related conditions (Hamilton Depression Scale score ≥ 17 points), or other unrelated serious mental disorders (schizophrenia, bipolar affective disorder or delirium) or serious neurological diseases (such as central nervous system infection (for example AIDS, syphilis), Creutzfeldt-Jakob disease, Huntington's chorea and primary Parkinson's disease,Lewy body dementia,corticobasal ganglia degeneration, brain trauma, epilepsy, brain tumors (with an exception of patients with meningioma which could not attribute to cognitive impairment based on the judgement of the researchers.)
- Those who use other drugs that affect the safety or efficacy evaluation of the tested drugs and disagree with withdrawal, such as NBP,cholinesterase inhibitors (Arizona, Essene, Galantamine, Huperzine A Tablets, Benzhexol Hydrochloride etc.), N-methyl-D-aspartic acid (NMDA) antagonists (such as Memantine, Amantadine, Ketamine, etc.);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Butylphthalide Soft CapsulesThe 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. | Drug | Butylphthalide Soft Capsules |
| placebo Soft CapsulesThe 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. | Drug | Placebo Soft Capsules |
Primary outcome
The occurrence of the composite endpoint
Time frame: 30 months
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
Change of CIBIC-Plus score
Time frame: 30 months
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.
Change of ADAS-cog score
Time frame: 30 months
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.
Volume changes of white matter hyperintensities observed on cerebral MRI
Time frame: 30 months
Nothing
7 secondary outcomes
The proportion of participants with an increase of mRS by≥ 2, or mRS≥5 for severe disability
Time frame: 30 months
The proportion of participants with new onset dementia。New onset dementia meets the following three criteria:
Time frame: 30 months
The proportion of participants with death due to any known or unknown cause
Time frame: 30 months
Changes of the gait speed in three-meter walktest
Time frame: 30 months
Changes in the number of silent brain infarcts
Time frame: 30 months
Changes in the number of cerebral microbleeds
Time frame: 30 months
Evolution of brain volumes (gray matter, white matter and CSF volumes)
Time frame: 30 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Butylphthalide Soft Capsules in people with Cerebral Small Vessel Diseases, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ruixin Pan (173 3112 8346, ly02034478@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The occurrence of the composite endpoint (time frame: 30 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2019; AzTrials last refreshed its copy on 7 Nov 2026.