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      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

      research-article
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      Alzheimer's Research & Therapy
      BioMed Central
      Sodium oligomannate, Efficacy, Safety, Alzheimer’s disease, Clinical trial

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          Abstract

          Background

          New 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.

          Methods

          We 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.

          Results

          A 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.

          Conclusions

          GV-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 registration

          ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13195-021-00795-7.

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          Most cited references45

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          A RATING SCALE FOR DEPRESSION

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            Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

            Neurology, 34(7), 939-939
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              The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia

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                Author and article information

                Contributors
                xiaoshifu@msn.com
                mygeng@simm.ac.cn
                wuzhangzhenxin@163.com
                Journal
                Alzheimers Res Ther
                Alzheimers Res Ther
                Alzheimer's Research & Therapy
                BioMed Central (London )
                1758-9193
                17 March 2021
                17 March 2021
                2021
                : 13
                : 62
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Geriatric Psychiatry, Shanghai Mental Health Center, , Shanghai Jiaotong University School of Medicine, ; Shanghai, China
                [2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Alzheimer’s Disease and Related Disorders Center, , Shanghai Jiaotong University, ; 600 South Wan Ping Road, Shanghai, 200030 China
                [3 ]GRID grid.413259.8, ISNI 0000 0004 0632 3337, Xuanwu Hospital Capital Medical University, ; Beijing, China
                [4 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Huashan Hospital, , Fudan University, ; Shanghai, China
                [5 ]GRID grid.452402.5, Qilu Hospital of Shandong University, ; Ji’nan, China
                [6 ]GRID grid.412901.f, ISNI 0000 0004 1770 1022, West China Hospital of Sichuan University, ; Chengdu, China
                [7 ]GRID grid.414906.e, ISNI 0000 0004 1808 0918, The First Affiliated Hospital of Wenzhou Medical University, ; Wenzhou, China
                [8 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, Guangzhou First People’s Hospital, School of Medicine, , South China University of Technology, ; Guangzhou, China
                [9 ]GRID grid.216938.7, ISNI 0000 0000 9878 7032, Tianjin Huanhu Hospital, , Huanhu Hospital Affiliated to Nankai University, ; Tianjin, China
                [10 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Geriatric Neurology of PLA General Hospital, ; Beijing, China
                [11 ]GRID grid.412645.0, ISNI 0000 0004 1757 9434, Department of Neurology, , Tianjin Medical University General Hospital, ; Tianjin, China
                [12 ]GRID grid.12981.33, ISNI 0000 0001 2360 039X, Sun Yat-Sen Memorial Hospital, , Sun Yat-Sen University, ; Guangzhou, China
                [13 ]GRID grid.411176.4, ISNI 0000 0004 1758 0478, Fujian Medical University Union Hospital, ; Fuzhou, China
                [14 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Neurology, Shanghai General Hospital, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, China
                [15 ]GRID grid.452438.c, Department of Neurology, , The First Affiliated Hospital of Xi’an Jiaotong University, ; Xi’an, China
                [16 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Neurology, Ruijin Hospital, , Shanghai Jiaotong University School of Medicine, ; Shanghai, China
                [17 ]GRID grid.414350.7, ISNI 0000 0004 0447 1045, Beijing Hospital, ; Beijing, China
                [18 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Psychiatry, Sir Run Run Shaw Hospital, , Zhejiang University School of Medicine and Key Laboratory of Medical Neurobiology of Zhejiang Province, ; Hangzhou, China
                [19 ]GRID grid.452743.3, ISNI 0000 0004 1788 4869, Northern Jiangsu People’s Hospital, ; Yangzhou, China
                [20 ]GRID grid.415954.8, ISNI 0000 0004 1771 3349, Department of Neurology, , China-Japan Friendship Hospital, ; Beijing, China
                [21 ]GRID grid.413810.f, Shanghai Changzheng Hospital, ; Shanghai, China
                [22 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Renji Hospital, , Shanghai Jiaotong University School of Medicine, ; Shanghai, China
                [23 ]GRID grid.413247.7, Department of Neurology, , Zhongnan Hospital of Wuhan University, ; Wuhan, China
                [24 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, Shandong Provinical Hospital affiliated to Shandong University, ; Ji’nan, China
                [25 ]Jiangsu Province People’s Hospital, Nanjing, China
                [26 ]GRID grid.411642.4, ISNI 0000 0004 0605 3760, Peking University Third Hospital, ; Beijing, China
                [27 ]GRID grid.452206.7, The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, China
                [28 ]Department of Geriatric psychiatry, Wuxi Mental Health Center, Wuxi, China
                [29 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Department of Neurology, Beijing Tiantan Hospital, , Capital Medical University, ; Beijing, China
                [30 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, The First Affiliated Hospital, , Zhejiang University School of Medicine, ; Hangzhou, China
                [31 ]GRID grid.412793.a, ISNI 0000 0004 1799 5032, Tongji Hospital of Tongji University, ; Shanghai, China
                [32 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Xiangya Hospital Central South University, ; Changsha, China
                [33 ]GRID grid.452666.5, ISNI 0000 0004 1762 8363, The Second Affiliated Hospital of Soochow University, ; Suzhou, China
                [34 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Beijing An Ding Hospital, , Capital Medical University, ; Beijing, China
                [35 ]GRID grid.413106.1, ISNI 0000 0000 9889 6335, Peking Union Medical College Hospital, ; No. 1 Shuaifuyuan, Beijing, 100730 China
                [36 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Med-X Research Institution, , Shanghai Jiao Tong University, ; Shanghai, China
                [37 ]Shanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China
                [38 ]GRID grid.418204.b, ISNI 0000 0004 0406 4925, Banner Alzheimer’s Institute, ; Phoenix, AZ USA
                [39 ]GRID grid.272362.0, ISNI 0000 0001 0806 6926, Chamberrs-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, , University of Nevada, ; Las Vegas, USA
                [40 ]GRID grid.9227.e, ISNI 0000000119573309, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, , Chinese Academy of Sciences, ; 555 Zu chong zhi Road, Nevada, China
                Author information
                http://orcid.org/0000-0002-4721-9646
                Article
                795
                10.1186/s13195-021-00795-7
                7967962
                33731209
                ae1b508e-0969-42ff-96a0-945b67848f91
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 12 November 2020
                : 22 February 2021
                Funding
                Funded by: National Science and Technology Major Project for Investigational New Drugs
                Award ID: 2011ZX09101-003-01
                Award ID: 2015ZX09101003
                Award ID: 2018ZX09711002-015
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Neurology
                sodium oligomannate,efficacy,safety,alzheimer’s disease,clinical trial
                Neurology
                sodium oligomannate, efficacy, safety, alzheimer’s disease, clinical trial

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