The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule

A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel, and Multi-centre Study to Evaluate the Clinical Efficacy and Safety of SaiLuoTong (SLT) in the Treatment of Vascular Dementia

As a traditional Chinese medicine compound, SaiLuoTong capsule is proven to have beneficial effects on learning and memory ability in animal models of vascular dementia (VaD). According to the result of the phase II study, the efficacy of SaiLuoTong capsule in the treatment of patients with VaD was better than that of placebo group and no difference in safety. So the study hypothesis is also that SaiLuoTong capsule will be effective in the treatment of patients with VaD and will be well tolerated. The purpose of the study is to confirm the efficacy and safety of SaiLuoTong capsule on patients with mild to moderate VaD. The outcome measures include general cognitive function, executive function, daily living skills, and mental behavior changes of symptoms in VaD patients.

Vascular dementia (VaD) is a clinical syndrome of acquired intellectual and functional impairment that results from cerebrovascular diseases. SaiLuoTong capsule is a traditional Chinese medicine compound; it is composed of ginseng extract (the main composition: ginseng total saponins), ginkgo biloba extract (the main composition: YinXingTong ester) and safflower extract (the main composition: the west safflower total glycosides). The function of SaiLuoTong capsule is Yiqi Huoxue and Huayu Tongluo in Chinese traditional medicine theory. Pharmacodynamics studies showed that SaiLuoTong capsule can significantly improve neurological symptoms caused by focal cerebral ischemia in animals, and learning and memory ability in animal models of VaD. The result of the phase II study showed that the efficacy of SaiLuoTong capsule in the treatment of patients with VaD was better than that of placebo group and no difference in safety. Based on these previous evidences, the investigators conduct this study to further confirm the efficacy and safety of SaiLuoTong capsule in patients with mild to moderate VaD. This study is a phase III clinical trial of SaiLuoTong capsule for treatment of vascular dementia. The study is a 52-week, multicentre, randomized, double -blind, placebo-controlled study.

Inclusion Criteria:

• 40 years≤Age≤75 years, female or male.
• With an education at more than (including) 6 years.
• Meet the diagnostic criteria for dementia in Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-V).
• Meet the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche etl'Enseignement en Neurosciences(NINDS-AIREN) Criteria of Probable Vascular Dementia (1993).
• MRI (magnetic resonance imaging) supports the presence of ischemic cerebrovascular disease, and meets NINDS-AIREN Imaging Criteria; the diameter of each infarct≤ 30mm(And the perivascular spaces and cerebral microbleeds were excluded).
• Modified Hachinski Ischemic (mHIS) Scale ≥ 4.
• Hamilton depression scale (HAMD) ≤ 17.
• Patients with mild or moderate VaD: 10 ≤ MMSE ≤ 26 and 1 ≤ CDR ≤ 2.
• Willing to participate in this study and could sign the informed consent form by him/herself and lawful guardian prior to the study.
• The subjects must have a care giver who are cognitively normal (MMSE scores: illiteracy> 17 points, 1 - 6 years of education > 20 points, 7 years and above of education > 24 points). 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. During the trial, a new caregiver must have MMSE score and the results would be presented in forms of subjects in the attachment.

Exclusion Criteria:

• Patients with dementia caused by a brain disease other than VaD (such as Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, Parkinson's disease, central nervous system demyelinative diseases, tumour, hydrocephalus, trauma, central nervous system infection, such as syphilis, AIDS and Creutzfeldt-Jakob disease);
• Patients with serious neurological impairment to finish the examination: hand hemiplegia, aphasia, and visual or hearing impairment.
• Laboratory anomalies: hemoglobin (Hb) level less than 80g/L , platelet count (Plt) level less than 50×109/L, activated partial thromboplastin time (APTT) exceeds 2.5 times the normal upper level, fibrinogen(FIB) level less than 0.5g/L, prothrombin time (PT) exceeds 2.5 times the normal upper level, Serum creatinine (Scr) exceeds 3 times the normal upper level, alanine aminotransferase (ALT) exceed 5 times the normal upper level , aspartate aminotransferase (AST) exceed 5 times the normal upper level, alkaline phosphates (ALP) exceed 5 times the normal upper level , γ-glutamyl transferase (γ-GT) exceed 5 times the normal upper level, total bilirubin (TBiL) exceeds 3 times the normal upper level.
• The subjects have nutritional and metabolic diseases and endocrine system diseases that cannot been controlled by therapy - thyroid diseases, parathyroid disease, vitamin or element deficiency.
• Patients with serious circulatory system diseases, respiratory system diseases, urinary system diseases, digestive system diseases, haemopoietic system diseases (such as unstable angina, uncontrollable asthma and active gastrorrhagia) and cancer.
• Serious mental disease (such as depression and schizophrenia) and epilepsy.
• Gastrointestinal diseases that may affect the absorption, distribution, and metabolism of the investigational drug.
• Alcohol and drug abuse.
• Patients who have been given any drug that can affect the cognitive function (including Chinese herbal preparations containing any one of these: ginseng, ginkgo leaf, and saffron; Western medicines such as donepezil, karbalatine, rivastigmine, huperzine a, memantine and similar drugs, etc; Butylphthalide and other drugs with the same effect such as runeirergine, aniracetam, cytosporine, dihydroergine, nimodipine, etc) within one month before the start of this study and cannot be discontinued.
• Patients who are allergic to more than 2 drugs or any component of the SLT capsules.
• Pregnant or lactating women.
• Patients who have participated in other clinical studies within 3 months prior to this study.
• Cannot accept magnetic resonance imaging (MRI) examination.