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Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia

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ClinicalTrials.gov Identifier: NCT03804229
Recruitment Status : Not yet recruiting
First Posted : January 15, 2019
Last Update Posted : May 15, 2019
Sponsor:
Collaborator:
CSPC-NBP Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Jianping Jia, Capital Medical University

Tracking Information
First Submitted Date  ICMJE January 11, 2019
First Posted Date  ICMJE January 15, 2019
Last Update Posted Date May 15, 2019
Estimated Study Start Date  ICMJE May 15, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
Vascular Dementia Assessment Scale-cognitive Subscale(VaDAS-cog) [ Time Frame: Change from baseline VaDAS-cog score at Week 52 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03804229 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
  • Clinician Interview Based Impression of Severity (CIBIC-plus) [ Time Frame: Change from baseline CIBIC-plus score at Week 52 ]
    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.
  • Alzheimer's Disease Co-operative Study Activities of Daily Living (ADCS-ADL) [ Time Frame: Change from baseline ADCS-ADL score at Week 52 ]
    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.
  • Neuropsychiatric Inventory (NPI) [ Time Frame: Change from baseline NPI score at Week 52 ]
    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.
  • Mini-mental State Examination (MMSE) [ Time Frame: Change from baseline MMSE score at Week 52 ]
    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.
  • MRI [ Time Frame: Change from baseline MRI at Week 52 ]
    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).
  • Blood biomarker [ Time Frame: Change from baseline concentration of BDNF and VEGF at Week 52 ]
    The concentration of BDNF and VEGF measured before the treatment, and at weeks 26 (± 7days) and 52 (±7 days) respectively.
  • MI/Cr ratio [ Time Frame: Change from baseline MI/Cr ratio at Week 52 ]
    The myoinositol (MI) and the creatine (Cr) levels (obtain the MI/Cr ratio) measured before the treatment, and at weeks 26 and 52 respectively.
  • Acetyl choline level [ Time Frame: Change from baseline concentration of acetyl choline at Week 52 ]
    The concentration of acetyl choline in the blood measured before the treatment, and at weeks 26 (± 7days) and 52 (± 7days) respectively.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Clinician Interview Based Impression of Severity (CIBIC-plus) [ Time Frame: Change from baseline CIBIC-plus score at Week 52 ]
    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.
  • Alzheimer's Disease Co-operative Study Activities of Daily Living (ADCS-ADL) [ Time Frame: Change from baseline ADCS-ADL score at Week 52 ]
    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.
  • Neuropsychiatric Inventory (NPI) [ Time Frame: Change from baseline NPI score at Week 52 ]
    The group difference in the difference between the Neuropsychiatric Inventory (NPI) scores at weeks 13 (±7 days), week 26 (±7 days), week 39 (±7 days) and week 52 (±7 days) and the baseline score.
  • Mini-mental State Examination (MMSE) [ Time Frame: Change from baseline MMSE score at Week 52 ]
    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.
  • MRI [ Time Frame: Change from baseline MRI at Week 52 ]
    The changes before and after the treatment at the cranial MRI bilateral hippocampus, the gyrus cinguli, the posteior 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).
  • Blood biomarker [ Time Frame: Change from baseline BDNF and VEGF levels at Week 52 ]
    BDNF and VEGF levels measured before the treatment, and at weeks 26 (± 7days) and 52 (±7 days) respectively.
  • MI/Cr ratio [ Time Frame: Change from baseline MI/Cr ratio at Week 52 ]
    The myoinositol (MI) and the creatine (Cr) levels (obtain the MI/Cr ratio) measured before the treatment, and at weeks 26 and 52 respectively.
  • Acetyl choline level [ Time Frame: Change from baseline acetyl choline level at Week 52 ]
    The acetyl choline level in the blood measured before the treatment, and at weeks 26 (± 7days) and 52 (± 7days) respectively.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
Official Title  ICMJE A Multi-center, Random, Double Blind and Placebo Control Phase III Clinical Study on the Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
Brief Summary 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.
Detailed Description 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Vascular Dementia
Intervention  ICMJE
  • Drug: Butylphthalide soft capsule
    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.
    Other Name: The effects of Butylphthalide soft capsule on VaD
  • Drug: Placebo soft capsule
    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.
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: active group
    Take two pills (100 mg each) of Butylphthalide soft capsule each time, three times a day, 0.5 hours before meal, taking with lukewarm water.
    Intervention: Drug: Butylphthalide soft capsule
  • Placebo Comparator: control group
    Take two pills of placebo soft capsule each time, three times a day, 0.5 hours before meal, taking with lukewarm water.
    Intervention: Drug: Placebo soft capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2019)
700
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Age ≥50 and ≤75, male or female.
  • 2. Formal education≥ 6 years.
  • 3. Meet the vascular dementia diagnosis criteria specified in the Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-V).
  • 4. Meet the vascular dementia diagnosis criteria specified in the Diagnostic and Statistical Manual of Mental Disorders - 4th Edition (DSM-IV).
  • 5. Meet the SIVD diagnosis criteria of Erkinjuntti.
  • 6. MRI supports the existence of an ischemic cerebrovascular disease; Meet the National Institute of Neurological Disorders and Stroke (NINDS-AIREN) imaging diagnosis criteria; The lesion located between supra-tentorial and subcortical areas; The maximum diameter of the infarction ≤30mm; The number of infarctions ≥3 and ≤5, and/or Fazekas score=2-3.
  • 7. The first ever ischemic stroke occurred within 6 months.
  • 8.The subjects are suffering from mild or moderate vascular dementia, with 11≤ MMSE ≤26, and the Clinical Dementia Rating (CDR) score 1≤ CDR ≤2.
  • 9. The Hamilton depression scale (HAMD) total score ≤17.
  • 10. The patient agrees to participate in this study and the patient or his or her legal guardian has signed the informed consent before the study.
  • 11. The subjects must have a care giver who has at least 6 years education with cognitively normal. The care giver shall also be able to take care of the patient at least 4 days a week for more than 4 hours a day while he or she can accompany the subjects to attend each visit.

Exclusion Criteria:

  • 1. Patients suffering from dementia caused by other cerebral diseases other than VaD (such as Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, Parkinson's disease, demyelinating diseases of the central nervous system, tumors, hydrocephalus, traumas, syphilis, AIDS, Creutzfeldt-Jakob disease, etc.); MRI indicates hippocampus or entorhinal cortex atrophy; and patients for whom VaD in combination with AD has been maximally excluded.
  • 2. Patients with severe neurologic impairments that hinder them from completing the required tests, such as hemiplegia of the convenient hand, various kinds of aphasia, and audio or visual disorders.
  • 3. Patients who cannot swallow any orally administered drugs, or who is suffering from any disease that can affect the absorption of orally administered drugs, such as active intestinal diseases, partial or complete intestinal obstruction.
  • 4. Patients suffering from severe diseases of the circulation system, the respiration system, the urinary system, the digestive system and the hemopoietic system (such as unstable angina pectoris, uncontrollable asthma and active gastric bleeding) and cancer.
  • 5. Patients suffering from nutritional and metabolic diseases and endocrine system disorders, such as thyroid disease, parathyroid disease and deficiency of vitamin or other elements.
  • 6. Patients suffering from severe mental diseases (such as depression and schizophrenia) and epilepsy.
  • 7. Patients with alcohol or drug abuse.
  • 8. Patients with a family history of dementia.
  • 9. Patients who have been given any drug that can affect the cognitive function, such as cholinergic drugs, antipsychotic drugs, antianxiety drugs, somnifacients and nootropic agents (including traditional Chinese herbal medicines and pills, such as cholinesterase inhibitors, memantine, Cenma Yizhi Capsules and Jiannaoan), for a long period of time (within 3 month before the start of this study and will continue using such drug).
  • 10. Patients who have used Butylphthalide soft capsule or injection within one month before grouping.
  • 11. Patients who are allergic to Butylphthalide/celery.
  • 12. Patients with severe bleeding tendency or hepatic dysfunction (with transaminase higher than 1.5 times of the normal upper limit).
  • 13. Pregnant or breast feeding women.
  • 14. Patients who have participated in other interference clinical studies within 3 months before grouping.
  • 15. Patients for whom MRI cranial imaging cannot be performed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jianping Jia, MD,PhD 0086-10 ext 83199449 jjp@ccmu.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03804229
Other Study ID Numbers  ICMJE CSPC-NBP-2018102
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jianping Jia, Capital Medical University
Study Sponsor  ICMJE Capital Medical University
Collaborators  ICMJE CSPC-NBP Pharmaceutical Co., Ltd.
Investigators  ICMJE
Principal Investigator: Jianping Jia, MD,PhD Xuanwu Hospital of Capital Medical University
PRS Account Capital Medical University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP