Clinical trial NCT03789760: The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vascular Dementia
Keywords: Vascular Dementia
cognitive
Lead sponsor: Shineway Pharmaceutical Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2018-12-31
Enrollment: 493
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Vascular Dementia Assessment Scale-cognitive Subscale(VaDAS-cog)
timeFrame: Change from baseline VaDAS-cog score at Week 52
measure: Alzheimer's Disease Cooperative Study-clinical Global Impression of Change(ADCS-CGIC)
timeFrame: Change from baseline ADCS-CGIC score at Week 52
Secondary outcomes:
measure: Alzheimer's Disease Cooperative Study-activities of Daily Living(ADCS-ADL)
timeFrame: Change from baseline ADCS-ADL score at Week 26
measure: Alzheimer's Disease Cooperative Study-activities of Daily Living(ADCS-ADL)
timeFrame: Change from baseline ADCS-ADL score at Week 52
measure: Mini-mental State Examination(MMSE)
timeFrame: Change from baseline MMSE score at Week 26
measure: Mini-mental State Examination(MMSE)
timeFrame: Change from baseline MMSE score at Week 52
measure: Clinical Dementia Rating(CDR Scale )
timeFrame: Change from baseline CDR Scale score at Week 26
measure: Clinical Dementia Rating(CDR Scale )
timeFrame: Change from baseline CDR Scale score at Week 52
measure: Clinical Dementia Rating sum of boxes(CDR-sb)
timeFrame: Change from baseline CDR-sb score at Week 26
measure: Clinical Dementia Rating sum of boxes(CDR-sb)
timeFrame: Change from baseline CDR-sb score at Week 52
measure: Blood biomarker: Brain-derived neurotrophic factor(BDNF)
timeFrame: Change from baseline BDNF at Week 26
measure: Blood biomarker: Brain-derived neurotrophic factor(BDNF)
timeFrame: Change from baseline BDNF at Week 52
measure: Blood biomarker: Vascular endothelial growth factor(VEGF)
timeFrame: Change from baseline VEGF at Week 26
measure: Blood biomarker: Vascular endothelial growth factor(VEGF)
timeFrame: Change from baseline VEGF at Week 52
measure: Blood biomarker: Matrix metalloproteinase-9(MMP-9)
timeFrame: Change from baseline MMP-9 at Week 26
measure: Blood biomarker: Matrix metalloproteinase-9(MMP-9))
timeFrame: Change from baseline MMP-9 at Week 52
measure: Blood biomarker: Interleukin-6(IL-6)
timeFrame: Change from baseline MMP-9 at Week 26
measure: Blood biomarker: Interleukin-6(IL-6)
timeFrame: Change from baseline MMP-9 at Week 52
measure: Vascular Dementia Assessment Scale-cognitive Subscale(VaDAS-cog)
timeFrame: Change from baseline VaDAS-cog score at week 13
measure: Vascular Dementia Assessment Scale-cognitive Subscale(VaDAS-cog)
timeFrame: Change from baseline VaDAS-cog score at week 26
measure: Vascular Dementia Assessment Scale-cognitive Subscale(VaDAS-cog)
timeFrame: Change from baseline VaDAS-cog score at week 39
measure: Alzheimer's Disease Cooperative Study-clinical Global Impression of Change(ADCS-CGIC)
timeFrame: Change from baseline ADCS-CGIC score at week 13
measure: Alzheimer's Disease Cooperative Study-clinical Global Impression of Change(ADCS-CGIC)
timeFrame: Change from baseline ADCS-CGIC score at week 26
measure: Alzheimer's Disease Cooperative Study-clinical Global Impression of Change(ADCS-CGIC)
timeFrame: Change from baseline ADCS-CGIC score at week 39
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuan Wu Hospital of Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Shougang Hospital
state: Beijing
city: Beijing
country: China
facility: Xiyuan Hospital
state: Beijing
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical College
state: Hebei
city: Handan
country: China
facility: Handan First Hospital
state: Hebei
city: Langfang
country: China
facility: Hebei Central Hospital of petrochina
state: Hebei
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The Fourth Hospital of Medical University
state: Hei Longjiang
city: Luoyang
country: China
facility: The First People's Hospital of Luoyang
state: Henan
city: Nanyang
country: China
facility: The First affiliated Hospital of Nanyang Medical college
state: Henan
city: Nanyang
country: China
facility: Nanyang Second People's Hospital
state: Henan
city: Changsha
country: China
facility: The First Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: Xiangya Boai Rehability Hospital
state: Hunan
city: Yueyang
country: China
facility: Yueyang Second People's Hospital
state: Hunan
city: Baotou
country: China
facility: Baogang Hospital
state: Inner Mongolia
city: Hohhot
country: China
facility: Inner Mongolia International Mongolian Hospital
state: Inner Mongolia
city: Taizhou
country: China
facility: Taizhou Hospital of Chinese Medicine
state: Jiangsu
city: Jiujiang
country: China
facility: Jiujiang University Clinical Medical College ▪ Jiujiang University Hospital
state: Jiangxi
city: Nanchang
country: China
facility: Nanchang Hongdu Hospital of TCM
state: Jiangxi
city: Changzhi
country: China
facility: Changzhi People's Hospital
state: Shanxi
city: Jinzhong
country: China
facility: Jinzhong First People's Hospital
state: Shanxi
city: Xianyang
country: China
facility: Xianyang Hospital of Yan'an University
state: Shanxi
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
state: Shanxi
city: Neijiang
country: China
facility: The Second people's Hospital of Neijiang
state: Sichuan
city: Tianjin
country: China
facility: Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine
state: Tianjin
city: Ürümqi
country: China
facility: The Second Hospital of Xingjiang Medical University
state: Xingjiang
city: Lishui
country: China
facility: The Central Hospital of Lishui City
state: Zhejiang
Study officials:
affiliation: Xuan Wu Hospital of Capital Medical University
name: Jianping Jia, Professor
role: PRINCIPAL_INVESTIGATOR
References: