{
  "abstract": "Background Cerebral small vessel disease (CSVD) represents a leading aetiology of vascular cognitive impairment, yet effective treatments for CSVD-related cognitive impairment (CSVD-CI) are limited. Although edaravone has shown potential in alleviating CSVD’s pathophysiological changes, its efficacy in CSVD-CI remains underexplored, partly due to the lack of a suitable long-term dosage form.Aim This trial aims to assess the efficacy and safety of edaravone sublingual tablets (EST) for cognitive impairment in patients with CSVD.Methods and design This multicentre, randomised, double-blind, placebo-controlled trial will enrol patients with CSVD-CI, randomly assigning them to receive either EST or placebo for 24 weeks of treatment with concurrent follow-up, followed by an additional 24-week post-treatment follow-up period. Cognitive function, safety, MRI-based CSVD burden, cerebral arterial endothelial function and immune-mediated inflammation will be assessed. The primary outcome is the between-group difference in Montreal Cognitive Assessment score changes from baseline to week 48, along with adverse event incidence. Secondary outcomes include changes in cognitive domain scores, CSVD burden, deep regional cerebral perfusion and levels of glial fibrillar acidic protein (GFAP), neurofilament light chain and inflammatory factors in peripheral blood from baseline to weeks 24 and 48.Discussion This trial will evaluate the efficacy and safety of EST in patients with CSVD-CI, potentially offering a new treatment strategy for this condition.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Qing Ye"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China"
      ],
      "name": "Weidong Ling"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Haifeng Chen"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Yue Cheng"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Lili Huang"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Yuting Mo"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Xin Zhang"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Linjie Yu"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Hailan Meng"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Lai Qian"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Rong Rong"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Xiaolei Zhu"
    },
    {
      "affiliations": [
        "Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China",
        "Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China",
        "State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, China",
        "Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China",
        "Nanjing Neurology Clinical Medical Center, Nanjing, China"
      ],
      "name": "Yun Xu"
    }
  ],
  "title": "Efficacy and safety of edaravone sublingual tablet for patients with cerebral small vessel disease-related cognitive impairment: study protocol for a multicentre, randomised, double-blind, placebo-controlled trial",
  "uid": "79c50714-5cad-5ed5-a491-3206058bdfa3"
}