<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03230071</url>
  </required_header>
  <id_info>
    <org_study_id>P2017-03-BDY-03-V03</org_study_id>
    <nct_id>NCT03230071</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia</brief_title>
  <official_title>Efficacy and Safety of Twice Daily TMBCZG in Mild to Moderate Vascular Dementia: Randomized, Double Blind, Parallel Group, Placebo Controlled, Multicenter Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dongzhimen Hospital, Beijing</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beijing Union pharmaceutical factory II</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Compete Medical Technology Development Co. Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dongzhimen Hospital, Beijing</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will be a 24-week multicentre, double-blind, placebo-controlled phase Ⅱa trial with&#xD;
      4 treatment arms in China. Participants aged 55-80 years will be randomized to TMBCZG-high&#xD;
      dose(84mg per day), TMBCZG- medium dose(56mg per day), TMBCZG- low dose(28mg per day) or to&#xD;
      placebo. The primary endpoint will be VADAS-Cog and CDR-SB. Secondary outcomes included&#xD;
      changes in MMSE and ADL. Patients' safety will be assessed by recording of adverse events,&#xD;
      clinical examinations, electrocardiography and laboratory tests. The patients, caregivers,&#xD;
      and investigators will be blinded to the treatment allocations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 28, 2017</start_date>
  <completion_date type="Actual">February 5, 2021</completion_date>
  <primary_completion_date type="Actual">August 22, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vascular Dementia Assessment Scale-cognitive subscale(VADAS-Cog)</measure>
    <time_frame>baseline, 4-week, 12-week, 24-week and 28-week.</time_frame>
    <description>Change from baseline to end of double-blind treatment of VADAS-Cog.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Dementia Rating-Sum of Boxes (CDR-SB)</measure>
    <time_frame>baseline, 4-week, 12-week, 24-week and 28-week.</time_frame>
    <description>Change from baseline to end of double-blind treatment of CDR-SB.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mini-Mental State Examination (MMSE)</measure>
    <time_frame>baseline, 4-week, 12-week, 24-week and 28-week.</time_frame>
    <description>Change from baseline to end of double-blind treatment of MMSE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activities of daily living (ADL)</measure>
    <time_frame>baseline, 4-week, 12-week, 24-week and 28-week.</time_frame>
    <description>Change from baseline to end of double-blind treatment of ADL.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Vascular Dementia</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo identified to TMBCZG,0.1g per pill which contains 0mg TMBCZG，3 pills per time, 2 times per day for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMBCZG-high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TMBCZG, 0.1g per pill which contains 14mg TMBCZG, 3 pills per time, 2 times per day for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMBCZG-medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMBCZG-low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMBCZG</intervention_name>
    <description>0.1g per pill which contains 14mg TMBCZG</description>
    <arm_group_label>TMBCZG-high dose</arm_group_label>
    <arm_group_label>TMBCZG-low dose</arm_group_label>
    <arm_group_label>TMBCZG-medium dose</arm_group_label>
    <other_name>TianMaBianChunZhiGanPian</other_name>
    <other_name>TianMaYouJiDuoSuanBianZhiGanPian(TMYJDSBZG)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>0.1g per pill which contains 0mg TMBCZG</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>TMBCZG-low dose</arm_group_label>
    <arm_group_label>TMBCZG-medium dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients meeting the clinical diagnosis of probable vascular dementia(VaD) established&#xD;
             according to the National Institute of Neurological Disorders and Stroke and the&#xD;
             Association Internationale pour la Recherche et l'Enseignement en Neurosciences&#xD;
             (NINDS-AIREN)were eligible to participate:&#xD;
&#xD;
               1. Dementia defined by clinical core criteria,&#xD;
&#xD;
               2. Cerebrovascular disease, defined by history of stroke, as well as multiple basal&#xD;
                  ganglia and white matter lacunes, or extensive periventricular white matter&#xD;
                  lesions( excluded medial temporal lobe atrophy or other special image),&#xD;
&#xD;
               3. A relationship between dementia and Cerebrovascular disease, manifested or&#xD;
                  inferred by the presence of one or more of the following: (a) onset of dementia&#xD;
                  within 3 months following a recognized stroke; (b) abrupt deterioration in&#xD;
                  cognitive functions; or fluctuating, stepwise progression of cognitive deficits.&#xD;
&#xD;
          -  Mild to Moderate Dementia with MMSE score of ≤26 and ≥11;&#xD;
&#xD;
          -  Aged ≥55 and ≤80 years old in both gender;&#xD;
&#xD;
          -  Weighing of ≥45kg and ≤90kg;&#xD;
&#xD;
          -  Adequate vision and hearing ability to complete all study tests;&#xD;
&#xD;
          -  With a stable caregiver.&#xD;
&#xD;
          -  Have a certain level of language competence (can read simple articles and write simple&#xD;
             sentences);&#xD;
&#xD;
          -  Informed consent, signed informed consent by legal guardian.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A medical history of other dementia types, like mixed dementia, Alzheimer's disease,&#xD;
             frontotemporal dementia, Parkinson's disease dementia, dementia with Lewy bodies,&#xD;
             Huntington disease, et al;&#xD;
&#xD;
          -  Subdural hematoma, traffic hydrocephalus, brain tumor, thyroid disease,vitamin&#xD;
             deficiency or other diseases which can lead to cognitive impediment;&#xD;
&#xD;
          -  Major depression (HAMD≥17) or major anxious(HAMA≥12);&#xD;
&#xD;
          -  Subject can't complete related test due to severe neurologic deficits, such as&#xD;
             hemiplegia, aphasia, audio-visual disorder and so forth;&#xD;
&#xD;
          -  Severe cardiovascular disease(severe arrhythmia, myocardial infarction within 3&#xD;
             months, New York Heart Association Functional Classification III-IV, systolic&#xD;
             pressure≥180mmHg or ≤90mmHg);&#xD;
&#xD;
          -  Severe liver or kidney dysfunction (alanine aminotransferase or aspartate transaminase&#xD;
             is more than 1.5 times the upper limit of normal, or serum creatinine is more than the&#xD;
             upper limit of normal);&#xD;
&#xD;
          -  Uncontrolled diabetes(glycosylated hemoglobin is more than 2 times the upper limit of&#xD;
             normal);&#xD;
&#xD;
          -  Asthma, chronic obstructive pulmonary disease, multiple neuritis, myasthenia gravis&#xD;
             and muscle atrophy;&#xD;
&#xD;
          -  Severe indigestion, gastrointestinal obstruction, gastric and duodenal ulcers and&#xD;
             other gastrointestinal disorders that can affect drug absorption;&#xD;
&#xD;
          -  A medical history of epileptic history, glaucoma, alcoholism, or psycho-substance&#xD;
             abuse;&#xD;
&#xD;
          -  Subject has been taking cholinesterase inhibitors, memantine, nimodipine or herbal&#xD;
             medicine with function of improving cognition in the past one month;&#xD;
&#xD;
          -  Use of sympathomimetic or antihistamines drugs within 48h before assessment;&#xD;
&#xD;
          -  Allergic constitution or allergic reactions to experimental drug;&#xD;
&#xD;
          -  According to the assessment of the investigator, subject cann't complete the study due&#xD;
             to poor compliance or other reasons;&#xD;
&#xD;
          -  Subject is participating in other clinical trials or participated in the past 1 month.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>JinZhou Tian, MD,PhD</last_name>
    <role>Study Director</role>
    <affiliation>Dongzhimen Hospital, Beijing University of Chinese Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dongzhimen Hospital ,Beijing University of Chinese Medicine</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100700</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>February 28, 2021</last_update_submitted>
  <last_update_submitted_qc>February 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dongzhimen Hospital, Beijing</investigator_affiliation>
    <investigator_full_name>Jinzhou Tian</investigator_full_name>
    <investigator_title>vice-president</investigator_title>
  </responsible_party>
  <keyword>Herbal therapy</keyword>
  <keyword>Randomized controlled trial</keyword>
  <keyword>Vascular Dementia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Dementia, Vascular</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03230071
org study id: P2017-03-BDY-03-V03
nct id: NCT03230071
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Vascular Dementia Assessment Scale-cognitive subscale(VADAS-Cog)
time frame: baseline, 4-week, 12-week, 24-week and 28-week.
description: Change from baseline to end of double-blind treatment of VADAS-Cog.
measure: Clinical Dementia Rating-Sum of Boxes (CDR-SB)
time frame: baseline, 4-week, 12-week, 24-week and 28-week.
description: Change from baseline to end of double-blind treatment of CDR-SB.
measure: Mini-Mental State Examination (MMSE)
time frame: baseline, 4-week, 12-week, 24-week and 28-week.
description: Change from baseline to end of double-blind treatment of MMSE.
measure: Activities of daily living (ADL)
time frame: baseline, 4-week, 12-week, 24-week and 28-week.
description: Change from baseline to end of double-blind treatment of ADL.
arm group label: Placebo
arm group type: Placebo Comparator
description: placebo identified to TMBCZG,0.1g per pill which contains 0mg TMBCZG，3 pills per time, 2 times per day for 24 weeks.
arm group label: TMBCZG-high dose
arm group type: Experimental
description: TMBCZG, 0.1g per pill which contains 14mg TMBCZG, 3 pills per time, 2 times per day for 24 weeks.
arm group label: TMBCZG-medium dose
arm group type: Experimental
description: 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.
arm group label: TMBCZG-low dose
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: TMBCZG
description: 0.1g per pill which contains 14mg TMBCZG
arm group label: TMBCZG-high dose
arm group label: TMBCZG-low dose
arm group label: TMBCZG-medium dose
other name: TianMaBianChunZhiGanPian
other name: TianMaYouJiDuoSuanBianZhiGanPian(TMYJDSBZG)
intervention type: Other
intervention name: placebo
description: 0.1g per pill which contains 0mg TMBCZG
arm group label: Placebo
arm group label: TMBCZG-low dose
arm group label: TMBCZG-medium dose
criteria: 
gender: All
minimum age: 55 Years
maximum age: 80 Years
healthy volunteers: No
last name: JinZhou Tian, MD,PhD
role: Study Director
affiliation: Dongzhimen Hospital, Beijing University of Chinese Medicine
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Dongzhimen Hospital, Beijing
investigator full name: Jinzhou Tian
investigator title: vice-president
mesh term: Dementia
mesh term: Dementia, Vascular
sharing ipd: No