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Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia

Primary Purpose

Vascular Dementia

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Tianzhi granule and placebo identified to donepezil
Donepezil and placebo identified to Tianzhi granule
Placebo
Sponsored by
Dongzhimen Hospital, Beijing
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vascular Dementia focused on measuring Vascular dementia, Tianzhi granule, Herbal medicine, Randomized controlled trial, Three arms

Eligibility Criteria

45 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Inpatients and outpatients meeting the diagnostic criteria probable VaD established according to the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) （DSM-Ⅳ） and the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN)were eligible to participate,
  • diagnosis of mild to moderate vascular dementia;
  • Chinese-speaking patients aged ≥45 and≤85 years old in both gender;
  • weighing between 45 and 90kg;
  • fully conscious;
  • MMSE score of≤26 and ≥14;
  • HIS score of ≥7;
  • adequate vision and hearing ability to complete all study tests;
  • with a stable caregiver.

Exclusion Criteria:

Patients will be excluded from the enrollment if they meet any of the followings:

  • a medical history of other dementia types, like Alzheimer's disease, Parkinson's disease dementia, Huntington disease, Normal pressure hydrocephalus, et al;
  • major depression (HAMD for 17 items>17) or psychotic disorder;
  • acute stage of cerebral hemorrhage or subarachnoid hemorrhage;
  • hypothyroidism;
  • drug or alcohol abuse;
  • epilepsy history; myasthenia gravis history;
  • severe cardiovascular disease(severe arrhythmia with heart rate≥100 or≤60 times per min, left bundle branch block, myocardial infarction within 3 months, systolic pressure≥180mmHg or ≤90mmHg);
  • severe liver or kidney dysfunction (alanine aminotransferase>60 IU/L, aspartate transaminase>60 IU/L or serum creatinine >266μmol/L);
  • severe asthma or chronic obstructive pulmonary disease;
  • gastrointestinal tract obstruction or severe peptic ulcer; glaucoma;
  • administration of cholinesterase inhibitors, memantine or nimodipine in the last month;
  • use of sympathomimetic agent, antihistamine drug, antianxiety drugs or tranquilizer within 48h before assessment;
  • use of antipsychotic drugs within 72h before assessment;
  • participation in other clinical trials; allergic history to any type of medication used in this study.

Sites / Locations

  • Dongzhimen Hospital,Beijing University of Chinese Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Tianzhi granule

Donepezil

Placebo

Arm Description

Tianzhi granule and placebo identified to donepezil

Donepezil and placebo identified to Tianzhi granule

Placebo identified toTianzhi granule and placebo identified to donepezil

Outcomes

Primary Outcome Measures

Changes of Vascular Dementia Assessment Scale-Cognitive Subscale(VADAS-cog) from baseline after 24 weeks' intervention
Cognition : VaDAS-cog is a revision of the ADAS-cog to be a better measure in vascular conditions. The original ADAS-cog developed by Rosen et al., measures cognitive performance by combining ratings of 11 items. The cognitive domains mainly addressed by ADAS-cog are memory (short term), language, ability to orientate (reflects memory), construction/planning of simple designs and performance. In addition to ADAS-cog, the VaDAS-cog comprises additional frontal lobe tests reflecting attention, working memory, executive function, and verbal fluency.The VADAS-cog will conducted at baseline, 4weeks, 12weeks, 24weeks
Changes of Clinician's Interview-Based Impression of Change-Plus carer Interview(CIBIC-plus) from baseline after 24 weeks' intervention
Overall clinical response: CIBIC-plus is a 7-point scale which provides an index of clinically important change for dementia patients. It is a global measure of detectable change in concentration, orientation, memory, language, behavior, initiative and activities of daily living, usually requiring separate interviews with patients and caregivers,the CIBIC-plus will be conducted at baseline, 4weeks, 12weeks, 24weeks

Secondary Outcome Measures

Changes of Mini-Mental State Examination(MMSE) from baseline after 24 weeks' treatment
Global cognition will be assessed by the MMSE,which will be conducted at baseline, 4weeks, 12weeks, 24weeks.
Changes of Activity of Daily Living Scale(ADL) from baseline after 24 week's intervention
Function:The ADL mainly used to measure the basic activities of daily living (or self-care) and the instrumental activities of daily living. The ADL scale can be divided to Physical Self-Maintenance Scale (PSMS) and the instrumental activities of daily living (IADL). The PSMS relate to physical activities, such as toileting, mobility, dressing and bathing , and the IADL contains 8 items ,such as shopping, cooking, doing laundry, handling finances, using telephone, mode of transportation, responsibility for own medication and housekeeping.The ADL wil be conducted baseline, 4weeks, 12weeks, 24weeks
Changes of Clock Drawing Test(CDT) from baseline after 24 week's intervention
Executive function and Visuospatial function : the CDT scale will be conducted at baseline, 4weeks, 12weeks, 24weeks.
Changes of Trail Making Test (TMT) from baseline after 24 week's intervention
Executive function: The TMT scale will be conducted at baseline, 4weeks, 12weeks, 24weeks.
Changes of Neuropsychiatric Inventory(NPI) from baseline after 24 weeks' intervention
Changes in psychological symptom: NPI is used throughout the study to assess changes in psychological symptom,the NPI will be conducted at baseline, 4 weeks, 12 weeks, 24 weeks.

Full Information

First Posted
May 19, 2015
Last Updated
January 5, 2020
Sponsor
Dongzhimen Hospital, Beijing
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1. Study Identification

Unique Protocol Identification Number
NCT02453932
Brief Title
Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
Official Title
A Phase III, Multicenter, Randomized, Double-blind, Positive /Placebo Controlled, Parallel, Three Arms Study of Tianzhi Granule in Mild to Moderate Vascular Dementia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dongzhimen Hospital, Beijing

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This ongoing study aimed to evaluate the efficacy and safety of Tianzhi granule in mild to moderate vascular dementia in a more reasonable design.
Detailed Description
This study is a 24-weeks, multicenter, randomized, double-blind, double- placebo, parallel controlled phase III trial being carried out in 23 centers around China. The study population includes mild to moderate VaD patients (planned a total of 630) aged 45-85 in both gender. Participants will be randomly allocated to TZK (15g/d) and placebo identified to donepezil, donepezil (5mg/d) and placebo identified to TZK, or placebo identified to TZK and placebo identified to donepezil for a 24-weeks double-blind treatment period . The primary outcome measure is change from baseline in the Vascular Dementia Assessment Scale-Cognitive Subscale and Clinician's Interview-Based Impression of Change-Plus carer Interview. The secondary outcomes are changes from baseline in the Mini-Mental State Examination, Activity of Daily Living Scale, Clock Drawing Test, Trail Making Test and Neuropsychiatric Inventory. Safety is being assessed by observing side effects and adverse reaction during the entire treatment period. Statistical analysis will be conducted according to per-protocol population and intend-to-treat population and the safety will be analyzed in safety set.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vascular Dementia
Keywords
Vascular dementia, Tianzhi granule, Herbal medicine, Randomized controlled trial, Three arms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
543 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tianzhi granule
Arm Type
Experimental
Arm Description
Tianzhi granule and placebo identified to donepezil
Arm Title
Donepezil
Arm Type
Active Comparator
Arm Description
Donepezil and placebo identified to Tianzhi granule
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo identified toTianzhi granule and placebo identified to donepezil
Intervention Type
Drug
Intervention Name(s)
Tianzhi granule and placebo identified to donepezil
Intervention Description
1 pack Tianzhi granule (5g), 3 times per day and placebo identified to donepezil, 1 pill per day for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Donepezil and placebo identified to Tianzhi granule
Intervention Description
donepezil 5mg per day and placebo identified to Tianzhi granule (5g, 3 times per day) for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo identified to Tianzhi granule (5g, 3 times per day) and placebo identified to donepezil ,1 pills per day for 24 weeks
Primary Outcome Measure Information:
Title
Changes of Vascular Dementia Assessment Scale-Cognitive Subscale(VADAS-cog) from baseline after 24 weeks' intervention
Description
Cognition : VaDAS-cog is a revision of the ADAS-cog to be a better measure in vascular conditions. The original ADAS-cog developed by Rosen et al., measures cognitive performance by combining ratings of 11 items. The cognitive domains mainly addressed by ADAS-cog are memory (short term), language, ability to orientate (reflects memory), construction/planning of simple designs and performance. In addition to ADAS-cog, the VaDAS-cog comprises additional frontal lobe tests reflecting attention, working memory, executive function, and verbal fluency.The VADAS-cog will conducted at baseline, 4weeks, 12weeks, 24weeks
Time Frame
week 0, 4, 12, 24
Title
Changes of Clinician's Interview-Based Impression of Change-Plus carer Interview(CIBIC-plus) from baseline after 24 weeks' intervention
Description
Overall clinical response: CIBIC-plus is a 7-point scale which provides an index of clinically important change for dementia patients. It is a global measure of detectable change in concentration, orientation, memory, language, behavior, initiative and activities of daily living, usually requiring separate interviews with patients and caregivers,the CIBIC-plus will be conducted at baseline, 4weeks, 12weeks, 24weeks
Time Frame
week 0, 4, 12, 24
Secondary Outcome Measure Information:
Title
Changes of Mini-Mental State Examination(MMSE) from baseline after 24 weeks' treatment
Description
Global cognition will be assessed by the MMSE,which will be conducted at baseline, 4weeks, 12weeks, 24weeks.
Time Frame
week 0, 4, 12, 24
Title
Changes of Activity of Daily Living Scale(ADL) from baseline after 24 week's intervention
Description
Function:The ADL mainly used to measure the basic activities of daily living (or self-care) and the instrumental activities of daily living. The ADL scale can be divided to Physical Self-Maintenance Scale (PSMS) and the instrumental activities of daily living (IADL). The PSMS relate to physical activities, such as toileting, mobility, dressing and bathing , and the IADL contains 8 items ,such as shopping, cooking, doing laundry, handling finances, using telephone, mode of transportation, responsibility for own medication and housekeeping.The ADL wil be conducted baseline, 4weeks, 12weeks, 24weeks
Time Frame
week 0, 4, 12, 24
Title
Changes of Clock Drawing Test(CDT) from baseline after 24 week's intervention
Description
Executive function and Visuospatial function : the CDT scale will be conducted at baseline, 4weeks, 12weeks, 24weeks.
Time Frame
week 0, 4, 12, 24
Title
Changes of Trail Making Test (TMT) from baseline after 24 week's intervention
Description
Executive function: The TMT scale will be conducted at baseline, 4weeks, 12weeks, 24weeks.
Time Frame
week 0, 4, 12, 24
Title
Changes of Neuropsychiatric Inventory(NPI) from baseline after 24 weeks' intervention
Description
Changes in psychological symptom: NPI is used throughout the study to assess changes in psychological symptom,the NPI will be conducted at baseline, 4 weeks, 12 weeks, 24 weeks.
Time Frame
week 0, 4, 12, 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Inpatients and outpatients meeting the diagnostic criteria probable VaD established according to the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) （DSM-Ⅳ） and the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN)were eligible to participate, diagnosis of mild to moderate vascular dementia; Chinese-speaking patients aged ≥45 and≤85 years old in both gender; weighing between 45 and 90kg; fully conscious; MMSE score of≤26 and ≥14; HIS score of ≥7; adequate vision and hearing ability to complete all study tests; with a stable caregiver. Exclusion Criteria: Patients will be excluded from the enrollment if they meet any of the followings: a medical history of other dementia types, like Alzheimer's disease, Parkinson's disease dementia, Huntington disease, Normal pressure hydrocephalus, et al; major depression (HAMD for 17 items>17) or psychotic disorder; acute stage of cerebral hemorrhage or subarachnoid hemorrhage; hypothyroidism; drug or alcohol abuse; epilepsy history; myasthenia gravis history; severe cardiovascular disease(severe arrhythmia with heart rate≥100 or≤60 times per min, left bundle branch block, myocardial infarction within 3 months, systolic pressure≥180mmHg or ≤90mmHg); severe liver or kidney dysfunction (alanine aminotransferase>60 IU/L, aspartate transaminase>60 IU/L or serum creatinine >266μmol/L); severe asthma or chronic obstructive pulmonary disease; gastrointestinal tract obstruction or severe peptic ulcer; glaucoma; administration of cholinesterase inhibitors, memantine or nimodipine in the last month; use of sympathomimetic agent, antihistamine drug, antianxiety drugs or tranquilizer within 48h before assessment; use of antipsychotic drugs within 72h before assessment; participation in other clinical trials; allergic history to any type of medication used in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinzhou Tian, MD,PhD
Organizational Affiliation
Dongzhimen Hospital, Beijing University of Chinese Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dongzhimen Hospital,Beijing University of Chinese Medicine
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100700
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
32054507
Citation
Shi J, Wei M, Ni J, Sun F, Sun L, Wang J, Yu T, Wang K, Lv P, Wang Y, Zhang Y, Gao X, Gao X, Luo B, Mao S, Zhang B, Ren X, Yu F, Hu W, Yin P, Wu N, Liu X, Bi Q, Wang Y, Tian J; CHASE Study Group. Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial. J Transl Med. 2020 Feb 13;18(1):76. doi: 10.1186/s12967-020-02232-z.
Results Reference
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Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia

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