Effects of Ninjin’yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial

Abstract

Purpose

To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin’yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD).

Patients and Methods

Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured.

Results

VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin’yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively).

Conclusion

Overall, Ninjin’yoeito significantly improved patients’ quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin’yoeito may improve frailty and sarcopenia in patients with COPD.

Keywords:

• clinical study
• frailty
• Ninjin’yoeito
• sarcopenia
• therapeutic effect

Institutional Review Board Statement

This study was conducted in accordance with the ethical principles detailed in the Declaration of Helsinki (revised in 2013) and the “Ethical Guidelines for Human Life Science and Medical Research Guidance (established on 16 April 2021)”. This study was approved by the Ethical Review Committee (Review Board of Human Rights and Ethics for Clinical Studies (HURECS, full accreditation from AAHRPP, CRB3200001) and Tokyo Medical and Dental University Certified Clinical Research Review Board (CRB3180020), approval number and date: jRCTs031210583, 11 January 2022). The registration data were managed using a subject identification code in accordance with the Personal Information Protection Law.

Data Sharing Statement

We have provided details in the paper regarding where the data supporting the reported results can be found.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study. The participants were fully debriefed on the content of the research trial and a written consent was obtained out of their own free will. Written informed consent was also obtained from the participants to publish this paper.

Acknowledgments

This research was funded by Kracie Pharmaceutical Ltd. (Tokyo, Japan). There are no other matters to be reported regarding the implementation of this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. Conceptualization, H.O.; methodology, H.O.; software, H.O. and S.K.; validation, K.O. and A.Y.; formal analysis, H.O. and S.K.; investigation, O.F. and M.A.; resources, S.K., O.F., and M.A.; data curation, K.O., A.Y., and M.A.; writing—original draft preparation, H.O.; writing—review and editing, S.K. and M.A.; visualization, H.O. and S.K.; supervision, O.F. and M.A.; project administration, K.O. and A.Y.; funding acquisition, H.O. and S.K. All authors have read and agreed to the published version of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.