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

• ClinicalTrials.gov Identifier: NCT01761227
• Recruitment Status: Completed
• First Posted: January 4, 2013
• Last Update Posted: October 23, 2018
• Sponsor: Dongzhimen Hospital, Beijing
• Collaborator: Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
• Information provided by (Responsible Party): Jinzhou Tian, Dongzhimen Hospital, Beijing

Tracking Information

• First Submitted Date: January 2, 2013
• First Posted Date: January 4, 2013
• Last Update Posted Date: October 23, 2018
• Actual Study Start Date: September 2012
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 2, 2013)

• 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 [ Time Frame: 24 weeks ]
  Global cognition was assessed with the CIBIC-plus, at baseline (day 1 clinic visit) and at 12-week intervals thereafter until week 24.
• Change in cognitive scores: Alzheimer Disease Assessment Scale-cognitive. subscale (ADAS-cog) [ Time Frame: 24 weeks ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 2, 2013)

• Change in functional scores: Activities of Daily Living (ADL). [ Time Frame: 24 weeks ]
  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).
• Change from baseline to the end of double-blind treatment in Mini-mental state examination (MMSE) scores [ Time Frame: 24 weeks ]
  Change in global cognition:Mini-mental state examination at baseline (day 1 clinic visit) and at 12-week intervals thereafter until week 24.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
• Official Title: 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.
• Brief Summary: 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).
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Vascular Dementia

Intervention

• 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
• Drug: Placebo
  Placebo for 3 tablets per time, 3 times per day for 24 weeks

Study Arms

• 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
  Intervention: Drug: Fufangdanshen Tablets
• 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
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 2, 2013): 240
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

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.
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01761227
• Other Study ID Numbers: SFDA2005L01916; SFDA【2008】I919
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Jinzhou Tian, Dongzhimen Hospital, Beijing
• Study 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

• PRS Account: Dongzhimen Hospital, Beijing
• Verification Date: October 2018