A phase II randomized trial of sodium oligomannate in Alzheimer’s dementia

• Main Authors: Tao Wang, Weihong Kuang, Wei Chen, Wenwei Xu, Liming Zhang, Yingjie Li, Hailin Li, Ying Peng, Yangmei Chen, Baojun Wang, Jinsong Xiao, Honghua Li, Chuanzhu Yan, Yifeng Du, Mouni Tang, Zhiyi He, Haibo Chen, Wei Li, Hong Lin, Shugui Shi, Jianzhong Bi, Huadong Zhou, Yan Cheng, Xiaoping Gao, Yihui Guan, Qiu Huang, Kewei Chen, Xianliang Xin, Jian Ding, Meiyu Geng, Shifu Xiao
• Format: Article
• Language: English
• Published: BMC 2020-09-01
• Series: Alzheimer’s Research & Therapy
• Subjects: Sodium oligomannate; Efficacy; Safety; Alzheimer’s disease; Clinical trial
• Online Access: http://link.springer.com/article/10.1186/s13195-020-00678-3

Abstract Background Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients. Methods The 24-week multicenter, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized in a 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer’s Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL, and NPI at 24 weeks after treatment compared with baseline. A subgroup study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements. Results Comparing with the placebo group (n = 83, change − 1.45), the ADAS-cog12 score change in the GV-971 600-mg group (n = 76) was − 1.39 (p = 0.89) and the GV-971 900-mg group (n = 83) was − 2.58 (p = 0.30). The treatment responders according to CIBIC-Plus assessment were significantly higher in the GV-971 900-mg group than the placebo group (92.77% vs. 79.52%, p < 0.05). The GV-971 900-mg subgroup showed a lower decline of cerebral metabolic rate for glucose than the placebo subgroup at the left precuneus, right posterior cingulate, bilateral hippocampus, and bilateral inferior orbital frontal at uncorrected p = 0.05. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%. Conclusions GV-971 was safe and well tolerated. GV-971 900 mg was chosen for phase III clinical study. Trial registration ClinicalTrials.gov, NCT01453569 . Registered on October 18, 2011.