Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia

The Safety and Efficacy of Fufangdanshen Tablets in Treatment of Mild to Moderate Vascular Dementia: a 24-week, Double Blind, Randomized, Parallel,Placebo Controlled Trial.

Purpose: The purpose of this study is to examine the efficacy and safety of Fufangdanshen Tablets in patients with mild to moderate vascular dementia (VaD).

Study Overview

• Status: Completed
• Conditions: Vascular Dementia
• Intervention / Treatment: Drug: Fufangdanshen Tablets; Drug: Placebo

Detailed Description

This multicenter, double-blind, placebo-controlled study will evaluate the safety and effectiveness of Fufangdanshen Tablets in patients with vascular dementia. All patients will initially receive placebo for a 2 weeks period and then will receive Fufangdanshen Tablets or placebo for 6 months. The primary measures of effectiveness include the change from baseline to the end of treatment in the ADAS-cog/11 score (Alzheimer's Disease Assessment Scale: sum of 11 cognitive items) and the CIBIC-plus score (Clinician's Interview Based Impression of Change - Plus Caregiver Input). Additional measures of effectiveness include the change from baseline to the end of the treatment in the MMSE score (Mini-mental State Examination), the ADL (Ability of Daily Living) score. Safety evaluations (incidence of adverse events, electrocardiograms (ECGs), physical examinations, laboratory tests) will be performed throughout the study. Patients who complete the double-blind portion of the study will be followed up 12 weeks. Effectiveness will be assessed at 12 weeks, 24weeks and 36 weeks. Safety evaluations (incidence of adverse events, ECGs, physical examinations, laboratory tests) will be performed at 12 weeks, 24weeks and 36 weeks of the study. The study hypothesis is that Fufangdanshen Tablets will be effective in the treatment of patients with vascular dementia and will be well tolerated. Double-blind: Fufangdanshen Tablets: 3 tablets per time, 3 times per day, and placebo : 3 tablets per time, 3 times per day. The placebo has similar smile and appearance as the Fufangdanshen Tablets.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100700
      • Dongzhimen Hospital ,Beijing University of Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.
• Weighing between 45 to 90 kg;
• The diagnosis had also to be compatible with the findings from a recent (within last 12 months) magnetic resonance image (MRI) of the brain and
• The Hachinski Ischemia Scale (HIS) score>4.
• six months' mild to moderate VaD duration before inclusion.
• Mild-to-moderate dementia (Score of the Mini-Mental State Examination (MMSE) defined as between 11 to 26)
• The Hamilton Depression Scale (HAMD for 17 items) had a score of ≤ 12
• have a consistent informant to accompany them on scheduled visits
• Ability to read, write, communicate, and understand cognitive testing instructions

Exclusion Criteria:

• Neurodegenerative disorders such as Parkinson's disease, with AD and any other secondary types of dementia;
• cognitive impairment resulting from conditions such as acute cerebral trauma, cerebral damage due to a lack of oxygen, vitamin deficiency, infections such as meningitis or AIDS, significant endocrine or metabolic disease, mental retardation, or a brain tumor
• having significant psychiatric disease, active peptic ulcer, clinically significant liver, kidney or lung disorders, or heart disease
• history of epilepsy, convulsions, drug abuse or alcohol abuse
• history of hypersensitivity to the treatment drugs;
• concomitant drugs with the potential to interfere with cognition;
• administration of other investigational drugs;
• females of child bearing potential without adequate contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fufangdanshen Tablets; 1 tablets contains contains tanshinoneⅡA 0.67mg , salvianolic acid B 8.2mg, Panax Notoginsenosides R1 0.53mg, ginsenoside Rb1 3.03mg, ginsenoside Rg1 2.73mg, 3 tablets per time, 3 times per day for 24 weeks	Drug: Fufangdanshen Tablets; 1 tablets contains contains tanshinoneⅡA 0.67mg , salvianolic acid B 8.2mg, Panax Notoginsenosides R1 0.53mg, ginsenoside Rb1 3.03mg, ginsenoside Rg1 2.73mg, 3 tablets per time, 3 times per day for 24 weeks
Placebo Comparator: Placebo; 3 tablets per time, 3 times per day for 24 weeks. The placebo has similar smile and appearance as the Fufangdanshen Tablets	Drug: Placebo; Placebo for 3 tablets per time, 3 times per day for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to end of double-blind treatment Clinician's Interview Based Impression of Change - Plus Caregiver Input; Alzheimer Disease Assessment Scale-cognitive subscale	Global cognition was assessed with the CIBIC-plus, at baseline (day 1 clinic visit) and at 12-week intervals thereafter until week 24.	24 weeks
Change in cognitive scores: Alzheimer Disease Assessment Scale-cognitive. subscale (ADAS-cog)	Cognition was assessed with the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), at baseline (day 1 clinic visit) and at 12-week intervals thereafter until week 24.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in functional scores: Activities of Daily Living (ADL).	Functional ability was evaluated with the ADL was evaluated at baseline (day 1 clinic visit), at the mid-study (week 12), and at the endpoint of treatment (week 24).	24 weeks
Change from baseline to the end of double-blind treatment in Mini-mental state examination (MMSE) scores	Change in global cognition:Mini-mental state examination at baseline (day 1 clinic visit) and at 12-week intervals thereafter until week 24.	24 weeks

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing
• Collaborators: Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
• Investigators: Principal Investigator: Jinzhou Tian, Ph.D, M.D, Dongzhimen Hospital, Beijing University of Chinese Medicine; Principal Investigator: Jing Shi, M.D, Dongzhimen Hospital, Beijing University of Chinese Medicine

Publications and helpful links

General Publications

• Tian J, Shi J, Wei M, Qin R, Ni J, Zhang X, Li T, Wang Y. The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial. Trials. 2016 Jun 8;17(1):281. doi: 10.1186/s13063-016-1410-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 2, 2013
• First Submitted That Met QC Criteria: January 2, 2013
• First Posted (Estimate): January 4, 2013

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: October 22, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Vascular dementia; Chinese Medicine; Fufangdanshen Tablets; Randomized Controlled trial
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Dementia; Dementia, Vascular
• Other Study ID Numbers: SFDA2005L01916; SFDA【2008】I919