FLUID study: study protocol for an open-label, single-centre pilot study to investigate the efFect of Lemborexant on sleep management in Japanese sUbjects aged 50 years and older with Insomnia Disorder.

Abstract

INTRODUCTION:

Bidirectional associations have been reported between sleep disturbance and both cognitive impairment, including Alzheimer's disease and amyloid beta-peptide (Aβ) accumulation. These relationships can be explained by the glymphatic system, which acts as a garbage drainage system in the brain. As interstitial fluid dynamics are suggested to increase during sleep, clearance of Aβ can be influenced by sleep disturbance or deprivation. We hypothesised that using lemborexant, an orexin receptor antagonist, to improve sleep quality would also improve the function of the glymphatic system. We plan to examine the effect of lemborexant on sleep quality and the glymphatic system among patients with insomnia disorder.

METHODS AND ANALYSIS:

This pilot study is designed as an open-label, single-arm, single-centre trial. Thirty patients aged 50 years and over with insomnia will be recruited. The participants will take lemborexant (5 mg) at bedtime for 12 weeks and undergo a home-based sleep study at baseline and weeks 4 and 12, as well as MRI examinations to evaluate the glymphatic system at baseline and week 12. The primary outcome will be changes in objective sleep parameters as evaluated using a sleep monitoring system. The secondary outcomes will be changes in subjective sleep parameters. The relationships between changes in sleep parameters and the glymphatic system will be evaluated using diffusion tensor image analysis along the perivascular space, which is called the ALPS-index. Sleep parameters and the ALPS-index will be analysed using a paired t-test or Pearson's correlation coefficient.

ETHICS AND DISSEMINATION:

The study protocol was approved by Nagoya University Certified Review Board. The findings from this research will be published in peer-reviewed journals and be presented at local, national and international conferences.

TRIAL REGISTRATION NUMBER:

jRCTs041210024.

• Authors: Ippei Okada, Kunihiro Iwamoto, Seiko Miyata, Akihiro Fujimoto, Masaki Tanaka, Manabu Amano, Nao Matsuyama, Toshiaki Taoka, Shinji Naganawa, Norio Ozaki
• Journal: BMJ open (BMJ Open) Vol. 11 Issue 11 Pg. e054885 (11 26 2021) ISSN: 2044-6055 [Electronic] England
• PMID: 34836909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Amyloid beta-Peptides
• Pyridines
• Pyrimidines
• lemborexant

Topics

• Aged
• Amyloid beta-Peptides
• Double-Blind Method
• Humans
• Japan
• Middle Aged
• Pilot Projects
• Pyridines
• Pyrimidines
• Sleep
• Sleep Initiation and Maintenance Disorders (drug therapy)
• Sleep Quality