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ID 116497
Author
Kondo, Takayuki Kyoto University
Banno, Haruhiko Kyoto University
Okunomiya, Taro Kyoto University
Amino, Yoko Kyoto University
Endo, Kayoko Kyoto University
Nakakura, Akiyoshi Kyoto University
Uozumi, Ryuji Kyoto University
Kinoshita, Akemi Kyoto University
Tada, Harue Kyoto University
Morita, Satoshi Kyoto University
Ishikawa, Hidehiro Mie University
Shindo, Akihiro Mie University
Yasuda, Ken Kyoto University
Taruno, Yosuke Kyoto University
Maki, Takakuni Kyoto University
Suehiro, Takashi Osaka University
Mori, Kohji Osaka University
Ikeda, Manabu Osaka University
Kanemaru, Kazutomi Tokyo Metropolitan Geriatric Medical Center
Ishii, Kenji Tokyo Metropolitan Institute of Gerontology
Shigenobu, Kazue Asakayama Hospital
Kutoku, Yumiko Kawasaki Medical School
Sunada, Yoshihide Kawasaki Medical School
Kawakatsu, Shinobu Fukushima Medical University
Shiota, Shunji Time Therapeutics
Watanabe, Toshifumi Time Therapeutics
Uchikawa, Osamu Towa Pharmaceutical
Takahashi, Ryosuke Kyoto University
Tomimoto, Hidekazu Mie University
Inoue, Haruhisa Kyoto University
Content Type
Journal Article
Description
Introduction
Alzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD.
Methods and analysis
This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted.
Ethics and dissemination
The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process.
Journal Title
BMJ Open
ISSN
20446055
Publisher
BMJ Publishing Group
Volume
11
Issue
6
Start Page
e051343
Published Date
2021-06-30
Rights
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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language
eng
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departments
University Hospital