{
  "abstract": "Introduction Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may have therapeutic effects against Parkinson’s disease (PD); however, clinical evidence has not yet been established and remains controversial. This clinical study aims to assess the efficacy, disease-modifying effects, safety and optimal dose of oral semaglutide tablets, a GLP-1 receptor agonist, in idiopathic patients with PD.Methods and analysis The MOST-ABLE study is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial of oral semaglutide tablets in 99 participants with PD. Patients with PD (Hoehn & Yahr stages 1–2.5) at eight sites in Japan will be randomly assigned in a 1:1:1 ratio to one of three groups: oral semaglutide tablets (7 mg or 14 mg) or placebo. The study drugs will be administered once daily as an add-on to conventional medical treatment for PD. After 36 weeks of treatment, the participants will be treated without the study drugs for 12 weeks. The efficacy outcomes include Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parkinson’s Disease Questionnaire-39, cognitive tests and dopamine transporter imaging. The primary endpoint is the change in the MDS-UPDRS part 3 score in the practically defined off-medication state from baseline at 48 weeks between the treatment allocation groups. The safety and tolerability will also be evaluated.Ethics and dissemination The study protocol was approved by the Pharmaceuticals and Medical Devices Agency of Japan and the study was approved by the institutional review boards at the University of Osaka Hospital and each study site. All participants are required to provide informed consent. The results will be disseminated in peer-reviewed journals, presented at scientific meetings and presented to patients in a lay summary format.Trial registration number jRCT2051230090 ( https://jrct.mhlw.go.jp/latest-detail/jRCT2051230090), universal trial number U1111-1271-3794.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, The University of Osaka Graduate School of Medicine, Suita, Japan"
      ],
      "name": "Yasuyoshi Kimura"
    },
    {
      "affiliations": [
        "Department of Medical Innovation, The University of Osaka Hospital, Suita, Japan"
      ],
      "name": "Toru Koda"
    },
    {
      "affiliations": [
        "Institute for Clinical and Translational Science, Nara Medical University, Kashihara, Japan"
      ],
      "name": "Hiroyuki Kurakami"
    },
    {
      "affiliations": [
        "Department of Medical Innovation, The University of Osaka Hospital, Suita, Japan"
      ],
      "name": "Shigeru Sakamoto"
    },
    {
      "affiliations": [
        "Department of Medical Innovation, The University of Osaka Hospital, Suita, Japan"
      ],
      "name": "Koji Iwasaki"
    },
    {
      "affiliations": [
        "Department of Neurology, The University of Osaka Graduate School of Medicine, Suita, Japan"
      ],
      "name": "Kanako Asai"
    },
    {
      "affiliations": [
        "Department of Neurology, The University of Osaka Graduate School of Medicine, Suita, Japan"
      ],
      "name": "Lindun Ge"
    },
    {
      "affiliations": [
        "Department of Advanced Radioisotope Medicine, Institute for Radiation Sciences, The University of Osaka, Suita, Japan"
      ],
      "name": "Hiroki Kato"
    },
    {
      "affiliations": [
        "Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan"
      ],
      "name": "Takashi Tsuboi"
    },
    {
      "affiliations": [
        "Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"
      ],
      "name": "Noriyuki Matsukawa"
    },
    {
      "affiliations": [
        "Department of Neurology, Toho University Faculty of Medicine, Tokyo, Japan"
      ],
      "name": "Osamu Kano"
    },
    {
      "affiliations": [
        "Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan",
        "Department of Neurology, Kyushu University Hospital, Fukuoka, Japan"
      ],
      "name": "Dai Matsuse"
    },
    {
      "affiliations": [
        "Department of Neurology, Hirosaki University School of Medicine, Hirosaki, Japan"
      ],
      "name": "Masahiko Tomiyama"
    },
    {
      "affiliations": [
        "Toyonaka Municipal Hospital, Toyonaka, Japan"
      ],
      "name": "Masaru Yokoe"
    },
    {
      "affiliations": [
        "Department of Neurology, Kindai University Faculty of Medicine, Osakasayama, Japan"
      ],
      "name": "Yoshitaka Nagai"
    },
    {
      "affiliations": [
        "Department of Neurology, The University of Osaka Graduate School of Medicine, Suita, Japan",
        "National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan"
      ],
      "name": "Hideki Mochizuki"
    }
  ],
  "title": "Disease-modifying effect, safety and optimal dose of oral semaglutide tablets for patients with Parkinson’s disease (MOST-ABLE study): protocol for a randomised, double-blind, placebo-controlled study",
  "uid": "25112386-d93b-589b-a92e-d70c34d1206a"
}