Effectiveness and Safety of Bu Shen Kai Qiao Fang in the Treatment of Alzheimer’s Disease: Study Protocol for a Multicenter, Prospective, Real-World Clinical Trial

Abstract

Background

Alzheimer’s disease (AD) is a common degenerative disease of the nervous system with serious impact on quality of life of patients and their families. With an aging population, AD has become a major public health problem in China and worldwide. However, the physiological and pathological mechanisms of AD have not been fully elucidated, and there is a lack of effective prevention and clinical treatment methods. Many studies have found that traditional Chinese medicine (TCM) has a good therapeutic effect on cognitive function in AD patients. Bu Shen Kai Qiao Fang (BSKQF) is one such Chinese herbal preparation used in the treatment of AD. We designed a protocol for a real-world clinical study of BSKQF combined with Donepezil hydrochloride (DH) to evaluate the efficacy and safety of this approach in the treatment of AD patients.

Methods

This is a protocol for a real-world, multicenter, prospective, observational cohort study. The study will recruit 860 AD patients from four hospitals across China. Equal numbers of patients will be treated with BSKQF and DH or with DH only. The criteria for grouping are based primarily on patient preference. Outcome measures include scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MOCA) and will be recorded at baseline, and at one, two and three months after enrollment. The plasma Aβ42 and plasma Tau levels of participating patients will also be measured by ELISA at baseline and after 3 months of treatment. Safety metrics and adverse events (AEs) of participating patients will be monitored and recorded.

Discussion

This study will evaluate the clinical efficacy and safety of BSKQF in the treatment of AD. The results will provide reliable evidence for the clinical application of BSKQF in the treatment of AD.

Study Registration

Trial registration: Chinese Clinical Trial Registry, NO. ChiCTR2000039670, Registered 5 November 2020 https://www.chictr.org.cn/showprojEN.html?proj=63800.

Keywords:

• Alzheimer’s disease
• Bu Shen Kai Qiao Fang
• real-world trial
• MMSE
• MOCA
• Aβ42
• tau

Abbreviations

AD, Alzheimer’s disease; BSKQF, Bu Shen Kai Qiao Fang; DH, Donepezil Hydrochloride; TCM, Traditional Chinese medicine; AEs, Adverse events; CRFs, Case report forms; Aβ, Amyloid β-protein; Tau, Microtubule-associated protein tau; EI, Efficacy indicator; RWR, Real world research; RCT, Randomized Controlled Trial; NTFs, Neurotrophic factors.

Data Sharing Statement

This is a research proposal, so there are currently no available data. Further information not included in this article will be provided by the corresponding author upon completion of the trial.

Ethical Approval and Consent to Participate

The protocol was approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (No. --2020SHL-KY-30) and other ethics committees at each center. In accordance with the Declaration of Helsinki, participants will not participate in the trial until written informed consent has been obtained. (The Informed Consent is shown in Supplementary Materials 1).

Consent for Publication

The trial results will be published in a peer-reviewed journal or presented at academic conferences. All participants contributing substantively to the trial are recognized in the form of granting authorship. Professional authors are not necessary.

Trial Status

Protocol version 2.0, June 2023. Patient enrollment began on July 6, 2021. Due to the recurrence of COVID-19, the recruitment of participating patients has been slow and is expected to be completed in June 2024.

Acknowledgments

The authors would like to thank all the staff and funders for their hard work in the development of this protocol and their efforts in its future implementation. We gratefully acknowledge the contributions of the following hospitals: (1) Shanghai Municipal Hospital of Traditional Chinese Medicine; (2) Shaanxi Provincial Hospital of Chinese Medicine; (3) The First Affiliated Hospital of Guangzhou University of Chinese Medicine; (4) Chengdu University of Traditional Chinese Medicine.

Disclosure

The authors declare that they have no conflicts of interest in this work.

Additional information

Funding

This study is supported by grants from the National Key R&D Program of China (NO. 2018YFC2002504) and the Three-Year Action Plan for Public Health 2020–2022 (Key Discipline Construction-TCM psychology/TCM psychiatry), and Shanghai Municipal Health Commission (GWV-10. 1-XK20). The funding sources have had no role in the study design and will not have a role in the execution, analyses, interpretation of the data, or decision to submit results.