As a traditional Chinese medicine compound, Yangxue Qingnao Pills is proven to have beneficial effects on learning and memory ability in animal models of Alzheimer's disease(AD). The purpose of the study is to evaluate the efficacy and safety of Yangxue Qingnao Pills on patients with mild to moderate AD. This phase II randomized, double-blind, parallel controlled trial include a 2 weeks run-in period, and a 48 weeks double-blind treatment period of after randomization. Participants will be randomly allocated to Yangxue Qingnao pills high dose group (7.5 g per time,2 times per day) ; and Yangxue Qingnao pills low dose group (5 g per time,2 times per day), or placebo group. The outcome measures include general cognitive function, ability of daily living, and behavioural and psychological symptoms in AD patients.
Yangxue Qingnao pills is a traditional Chinese herbal medicine, which is composed of Angelicae Sinensis Radix , Chuanxiong Rhizoma , Paeoniae Radix Alba, Rehmannia glutinosa, Uncaria macrophylla Wall, Caulis spatholobi, Spica Prunellae, Catsia tora Linn , Mater Margarita, Corydalis ambigua and Asarum sieboldii. The function of Yangxue Qingnao pills is nourishing blood and calming liver, promoting blood circulation and dredging collaterals in Chinese traditional medicine theory. This study is a 48-weeks, multicenter, randomized, double-blind, parallel controlled phase II trial being carried out in China. The study population includes mild to moderate Alzheimer's disease (planned a total of 216) aged 65-85 in both gender. Participants will be randomly allocated to Yangxue Qingnao pills high dose group (7.5 g per time,2 times per day) ; and Yangxue Qingnao pills low dose group (5 g per time,2 times per day), or placebo group for a 48-weeks double-blind treatment period. The primary outcome measure is change from baseline in the Alzheimer's Disease Assessment Scale- Cognition Subscale (ADAS-cog) and the clinical dementia rating scale. The secondary outcomes are changes from baseline in the Mini-Mental State Examination(MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL/24) and Neuropsychiatric Inventory. Besides, the blood biomarkers including Aβ42, Aβ40, T-tau, P-tau181, NfL, TOM1, IL-1R1,IL-1b, IL-6, IL-8, TNF-a, FB, FH, sCR1, MCP-1, eotaxin-1, Ach, ChEI and the hippocampal volume on MRI. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
216
72 subjects in the Yangxue Qingnao pills group take 7.5g of Yangxue Qingnao pills each time, twice a day, 0.5 hours after breakfast and dinner, taking with warm water.
72 subjects in the Yangxue Qingnao pills group take 5g of Yangxue Qingnao pills and 2.5g placebo identified to Yangxue Qingnao pills each time, twice a day, 0.5 hours after breakfast and dinner, taking with warm water.
72 subjects in the placebo group take 7.5g placebo identified to Yangxue Qingnao pills each time, twice a day, 0.5 hours after breakfast and dinner, taking with warm water.
Dongzhimen Hospital ,Beijing University of Chinese Medicine
Beijing, Beijing Municipality, China
RECRUITINGAlzheimer's Disease Assessment Scale- Cognition Subscale (ADAS-cog)
The Alzheimer's Disease Assessment Scale-Cognitive Subscale test is one of the most frequently used tests to measure cognition in research studies and clinical trials for new drugs and other interventions.The ADAS-Cog consists of 11 parts and takes approximately 30 minutes to administer.The test administrator adds up points for the errors in each task of the ADAS-Cog for a total score ranging from 0 to 70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.
Time frame: Change from baseline ADAS-cog score at Week 48
Clinical dementia rating scale-sum box(CDR-SB)
The Clinical Dementia Rating Scale (CDR) is a global assessment instrument that yields global and Sum of Boxes (CDR-SB) scores, with the global score regularly used in clinical and research settings to stage dementia severity. The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18. Higher score means severe global cognition impairment.
Time frame: Change from baseline CDR-SB score at Week 48
Mini-Mental State Examination(MMSE)
TThe Mini-Mental Status Examination offers a quick and simple way to quantify cognitive function and screen for cognitive loss. It tests the individual's orientation, attention, calculation, recall, language and motor skills. It takes \~ 5-10 minutes to administer The range for the total MMSE score is 0 to 30, higher score means better cognition.
Time frame: Change from baseline MMSE score at Week 48
Neuropsychiatric Inventory(NPI)
The NPI is a semistructured clinician interview of caretakers in which the severity and frequency of disturbance in 12 symptom domains is rated
Time frame: Change from baseline NPI score at Week 48
Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL/23)
The Alzheimer's Disease Cooperative Study (ADCS) tested 23-item version (ADCS-ADL/23) includes more complex ADL for the assessment of mild to moderate AD, such as reading books or magazines, pastime activities, or household chores. Ratings take about 20 minutes and are based on information obtained from the patient and caregiver. The scores range from 0 to 78, higher scores indicating less functional impairment.
Time frame: Change from baseline ADCS-ADL/23 score at Week 48
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