PMID- 35547390
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220516
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 13
DP  - 2022
TI  - Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica 
      Spectrum Disorder (hUC-MSC-NMOSD): A Study Protocol for a Prospective, 
      Multicenter, Randomized, Placebo-Controlled Clinical Trial.
PG  - 860083
LID - 10.3389/fneur.2022.860083 [doi]
LID - 860083
AB  - BACKGROUND: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing 
      and disabling autoimmune disease of the central nervous system. Its optimal 
      first-line treatment to reduce relapse rate and ameliorate neurological 
      disability remains unclear. We will conduct a prospective, multicenter, 
      randomized, placebo-controlled clinical trial to study the safety and 
      effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in 
      treating NMOSD. METHODS: The trial is planned to recruit 430 AQP4-IgG 
      seropositive NMOSD patients. It consists of three consecutive stages. The first 
      stage will be carried out in the leading center only and aims to evaluate the 
      safety of hUC-MSCs. Patients will be treated with three different doses of 
      hUC-MSCs: 1, 2, or 5 x 10(6) MSC/kg.weight for the low-, medium-, and high-dose 
      group, respectively. The second and third stages will be carried out in six 
      centers. The second stage aims to find the optimal dosage. Patients will be 
      1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled 
      group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 
      randomized into the optimal dose and the controlled group. The primary endpoint 
      is the first recurrent time and secondary endpoints are the recurrent times, EDSS 
      scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. 
      Endpoint events and side effects will be evaluated every 3 months for 2 years. 
      DISCUSSION: Although hUC-MSC has shown promising treatment effects of NMOSD in 
      preclinical studies, there is still a lack of well-designed clinical trials to 
      evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as 
      we know, this trial will be the first one to systematically demonstrate the 
      clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to 
      determine the optimal dose of hUC-MSC for NMOSD patients. TRIAL REGISTRATION: The 
      study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 
      2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial 
      protocol (Protocol version 1.2.1) was released on 16 March 2020.
CI  - Copyright (c) 2022 Yao, Xie, Cai, Zhang, Deng, Gao, Wang, Xu, Ding, Wu, Zhao, Wang, 
      Song, Wang, Xie, Li, Wan, Lin, Jin, Wang, Qiu, Zhuang, Zhou, Jin, Ni, Yan, Guo, 
      Xue, Qian and Guan.
FAU - Yao, Xiao-Ying
AU  - Yao XY
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Xie, Li
AU  - Xie L
AD  - Clinical Research Center, School of Medicine, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Cai, Yu
AU  - Cai Y
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Deng, Ye
AU  - Deng Y
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Gao, Mei-Chun
AU  - Gao MC
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Wang, Yi-Shu
AU  - Wang YS
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Xu, Hui-Ming
AU  - Xu HM
AD  - State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Clinical Stem 
      Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Ding, Jie
AU  - Ding J
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Wu, Yi-Fan
AU  - Wu YF
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhao, Nan
AU  - Zhao N
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Wang, Ze
AU  - Wang Z
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Song, Ya-Ying
AU  - Song YY
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Wang, Li-Ping
AU  - Wang LP
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Xie, Chong
AU  - Xie C
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Li, Ze-Zhi
AU  - Li ZZ
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Wan, Wen-Bin
AU  - Wan WB
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Lin, Yan
AU  - Lin Y
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Jin, Hai-Feng
AU  - Jin HF
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Wang, Kan
AU  - Wang K
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Qiu, Hui-Ying
AU  - Qiu HY
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhuang, Lei
AU  - Zhuang L
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhou, Yan
AU  - Zhou Y
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Jin, Yu-Yan
AU  - Jin YY
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Ni, Li-Ping
AU  - Ni LP
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Yan, Jia-Li
AU  - Yan JL
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Guo, Quan
AU  - Guo Q
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Xue, Jia-Hui
AU  - Xue JH
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Qian, Bi-Yun
AU  - Qian BY
AD  - Clinical Research Center, School of Medicine, Shanghai Jiao Tong University, 
      Shanghai, China.
AD  - Shanghai Clinical Research Promotion and Development Center, Shanghai Hospital 
      Development Center, Shanghai, China.
FAU - Guan, Yang-Tai
AU  - Guan YT
AD  - Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20220425
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC9082633
OTO - NOTNLM
OT  - human umbilical cord mesenchymal stem cell (hUC-MSC)
OT  - multicenter trial
OT  - neuromyelitis optica spectrum disorder (NMOSD)
OT  - randomized controlled trial
OT  - study protocol
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/14 06:00
MHDA- 2022/05/14 06:01
PMCR- 2022/04/25
CRDT- 2022/05/13 11:12
PHST- 2022/01/22 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/05/13 11:12 [entrez]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/05/14 06:01 [medline]
PHST- 2022/04/25 00:00 [pmc-release]
AID - 10.3389/fneur.2022.860083 [doi]
PST - epublish
SO  - Front Neurol. 2022 Apr 25;13:860083. doi: 10.3389/fneur.2022.860083. eCollection 
      2022.