Evidence map›Paper›PMID 33731209›Full record

Trial reportAlzheimer's research & therapy2021

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

Shifu Xiao, Piu Chan, Tao Wang, Zhen Hong, Shuzhen Wang, Weihong Kuang, Jincai He, Xiaoping Pan, Yuying Zhou, Yong Ji and 75 more

Abstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

118 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.The New England journal of medicine · 2023
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58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

85 authors.

Shifu Xiao *Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China. xiaoshifu@msn.com.ORCID 0000-0002-4721-9646
Piu Chan *Xuanwu Hospital Capital Medical University, Beijing, China.
Tao Wang *Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhen HongHuashan Hospital, Fudan University, Shanghai, China.
Shuzhen WangQilu Hospital of Shandong University, Ji'nan, China.
Weihong KuangWest China Hospital of Sichuan University, Chengdu, China.
Jincai HeThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Xiaoping PanGuangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Yuying ZhouTianjin Huanhu Hospital, Huanhu Hospital Affiliated to Nankai University, Tianjin, China.
Yong JiTianjin Huanhu Hospital, Huanhu Hospital Affiliated to Nankai University, Tianjin, China.
Luning WangDepartment of Geriatric Neurology of PLA General Hospital, Beijing, China.
Yan ChengDepartment of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
Ying PengSun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Qinyong YeFujian Medical University Union Hospital, Fuzhou, China.
Xiaoping WangDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuncheng WuDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qiumin QuDepartment of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Shengdi ChenDepartment of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shuhua LiBeijing Hospital, Beijing, China.
Wei ChenDepartment of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and Key Laboratory of Medical Neurobiology of Zhejiang Province, Hangzhou, China.
Jun XuNorthern Jiangsu People's Hospital, Yangzhou, China.
Dantao PengDepartment of Neurology, China-Japan Friendship Hospital, Beijing, China.
Zhongxin ZhaoShanghai Changzheng Hospital, Shanghai, China.
Yansheng LiRenji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Junjian ZhangDepartment of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yifeng DuShandong Provinical Hospital affiliated to Shandong University, Ji'nan, China.
Weixian ChenJiangsu Province People's Hospital, Nanjing, China.
Dongsheng FanPeking University Third Hospital, Beijing, China.
Yong YanThe First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiaowei LiuDepartment of Geriatric psychiatry, Wuxi Mental Health Center, Wuxi, China.
Wei ZhangDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Benyan LuoThe First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Wenyuan WuTongji Hospital of Tongji University, Shanghai, China.
Lu ShenXiangya Hospital Central South University, Changsha, China.
Chunfeng LiuThe Second Affiliated Hospital of Soochow University, Suzhou, China.
Peixian MaoBeijing An Ding Hospital, Capital Medical University, Beijing, China.
Qiumei WangPeking Union Medical College Hospital, No. 1 Shuaifuyuan, Beijing, 100730, China.
Qianhua ZhaoHuashan Hospital, Fudan University, Shanghai, China.
Qihao GuoHuashan Hospital, Fudan University, Shanghai, China.
Yongtao ZhouXuanwu Hospital Capital Medical University, Beijing, China.
Yi LiQilu Hospital of Shandong University, Ji'nan, China.
Lijun JiangWest China Hospital of Sichuan University, Chengdu, China.
Wenwei RenThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Yingjun OuyangGuangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Yan WangTianjin Huanhu Hospital, Huanhu Hospital Affiliated to Nankai University, Tianjin, China.
Shuai LiuTianjin Huanhu Hospital, Huanhu Hospital Affiliated to Nankai University, Tianjin, China.
Jianjun JiaDepartment of Geriatric Neurology of PLA General Hospital, Beijing, China.
Nan ZhangDepartment of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
Zhonglin LiuSun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Raoli HeFujian Medical University Union Hospital, Fuzhou, China.
Tingyi FengDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wenhui LuDepartment of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Huidong TangDepartment of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Ping GaoBeijing Hospital, Beijing, China.
Yingchun ZhangDepartment of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and Key Laboratory of Medical Neurobiology of Zhejiang Province, Hangzhou, China.
Lanlan ChenNorthern Jiangsu People's Hospital, Yangzhou, China.
Lei WangDepartment of Neurology, China-Japan Friendship Hospital, Beijing, China.
You YinShanghai Changzheng Hospital, Shanghai, China.
Qun XuRenji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Jinsong XiaoDepartment of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Lin CongShandong Provinical Hospital affiliated to Shandong University, Ji'nan, China.
Xi ChengJiangsu Province People's Hospital, Nanjing, China.
Hui ZhangPeking University Third Hospital, Beijing, China.
Dan GaoThe First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Minghua XiaDepartment of Geriatric psychiatry, Wuxi Mental Health Center, Wuxi, China.
Tenghong LianDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Guoping PengThe First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xu ZhangTongji Hospital of Tongji University, Shanghai, China.
Bin JiaoXiangya Hospital Central South University, Changsha, China.
Hua HuThe Second Affiliated Hospital of Soochow University, Suzhou, China.
Xueyan ChenBeijing An Ding Hospital, Capital Medical University, Beijing, China.
Yihui GuanHuashan Hospital, Fudan University, Shanghai, China.
Ruixue CuiPeking Union Medical College Hospital, No. 1 Shuaifuyuan, Beijing, 100730, China.
Qiu HuangMed-X Research Institution, Shanghai Jiao Tong University, Shanghai, China.
Xianliang XinShanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China.
Hongjian ChenShanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China.
Yu DingShanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China.
Jing ZhangShanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China.
Teng FengShanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China.
Marc CantillonShanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China.
Kewei ChenBanner Alzheimer's Institute, Phoenix, AZ, USA.
Jeffrey L CummingsChamberrs-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, USA.
Jian DingState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu chong zhi Road, Nevada, China.
Meiyu GengState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu chong zhi Road, Nevada, China. mygeng@simm.ac.cn.
Zhenxin ZhangPeking Union Medical College Hospital, No. 1 Shuaifuyuan, Beijing, 100730, China. wuzhangzhenxin@163.com.

Funding

Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
NVEDARC Clinical CoreP20AG068053 · NIA · CLEVELAND CLINIC FOUNDATION · PI FOX, ROBERT J. · 2020 to 2022
$3.3M
NIA NIH HHS P20 AG068053NIGMS NIH HHS P20 GM109025
6 · The paper itself

Abstract

backgroundNew therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.

methodsWe conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored.

resultsA total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.

conclusionsGV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated.

trial registrationClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.

Indexed as

Alzheimer DiseasePharmaceutical PreparationsActivities of Daily LivingChinaCholinesterase InhibitorsDouble-Blind MethodHumansMannoseOligosaccharidesSodiumTreatment OutcomeCholinesterase InhibitorsGV-971MannoseOligosaccharidesPharmaceutical PreparationsSodiumAlzheimer’s diseaseClinical trialEfficacySafetySodium oligomannate

Identifiers

PMID33731209
PMCPMC7967962

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.