Shifu Xiao1,2, Tao Wang1,2, Xiuqiang Ma3, Yingyi Qin3, Xia Li1, Zhongxin Zhao4, Xueyuan Liu5, Xiaoping Wang6, Hengge Xie7, Qinpu Jiang8, Li Sun9, Benyan Luo10, Lan Shang11, Weixian Chen12, Yan Bai13, Muni Tang14, Maolin He15, Lan Wu16, Qilin Ma17, Deren Hou18, Jia He3. 1. Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. Alzheimer's Disease and Related Disorders Center, Shanghai Jiaotong University, Shanghai, China. 3. Department of Health Statistics, The Second Military Medical University, Shanghai, China. 4. Department of Neurology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. 5. Department of Neurology, The 10th People's Hospital, Tongji University, Shanghai, China. 6. Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China. 7. Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, China. 8. Mental Health Center of Hebei Province, Baoding, Hebei Province, China. 9. Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, China. 10. Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. 11. Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China. 12. Department of Geratology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. 13. Department of psychiatry, First Affiliated Hospital of Kunming Medicine University, Kunming, Yunnan Province, China. 14. Guangzhou Psychiatric Hospital, Guangzhou, Guangdong Province, China. 15. Department of Neurology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. 16. Department of Neurology, Affiliated Hospital of Guilin Medical School, Guilin, Guangxi Province, China. 17. Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China. 18. Neurological Department, The Third Xiangya Hospital of Central South University, Hunan Province, China.
Abstract
Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ andADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.
RCT Entities:
Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.