Table_1_Efficacy of acupuncture in patients with mild Alzheimer’s disease and its impact on gut microbiota: Study protocol for a randomized sham-controlled trial.PDF

IntroductionAcupuncture is used as an adjuvant therapy for Alzheimer’s disease (AD), but available evidence for efficacy is limited so far. Growing studies suggest that resident gut microbiota contributes to the development and progression of AD. Meanwhile, acupuncture is reported to treat gastrointestinal and neurodegenerative disorders via the gut-brain axis. Therefore, our aim is to confirm the adjunctive therapeutic effects of acupuncture for AD, and explore the relationship between clinical efficacy and shifts of gut microbiota.
Methods and analysisThis is a randomized, participant-masked, sham-controlled trial. One hundred and sixty participants with mild AD will be randomly assigned (1:1) to either active acupuncture or non-penetrating sham acupuncture (three times weekly for 14 weeks) added to donepezil treatment (5 mg per day for 28 weeks). The primary efficacy outcome is the change from baseline to week 28 in the Alzheimer’s disease Assessment Scale (ADAS-cog12). Secondary efficacy outcomes include other assessments of the Mini-Mental State Examination (MMSE), the Alzheimer’s disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI). Gut microbiota will be measured using 16S rRNA tag sequencing.
DiscussionThis rigorous trial will provide high-quality evidence on the efficacy of acupuncture as adjunctive treatment for mild AD, and identify the possible mechanisms of acupuncture from gut microbiota.
Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT05078944], ClinicalTrials.gov [NCT05078944]. Registered 15 October 2021

引言
针灸目前被用作阿尔茨海默病（Alzheimer’s disease, AD）的辅助治疗手段，但迄今相关疗效证据仍较为有限。越来越多的研究表明，肠道常驻菌群参与阿尔茨海默病的发生与进展过程；同时有研究证实，针灸可通过肠-脑轴（gut-brain axis）治疗胃肠道疾病及神经退行性疾病。因此本研究旨在明确针灸对轻度阿尔茨海默病的辅助治疗效果，并探讨临床疗效与肠道菌群结构改变之间的关联。

方法与分析
本研究为一项随机、受试者设盲、假对照临床试验。将160例轻度阿尔茨海默病患者按1:1的比例随机分配至活性针灸组与非穿透性假针刺组，两组均联合多奈哌齐治疗（每日5mg，持续28周），针灸或假针刺操作频率为每周3次，共持续14周。本研究的主要疗效终点为基线至第28周时阿尔茨海默病评定量表（ADAS-cog12）的评分变化。次要疗效终点包括简易精神状态检查表（MMSE）、阿尔茨海默病协作研究日常活动能力量表（ADCS-ADL）及神经精神问卷（NPI）的相关评估结果。肠道菌群将通过16S rRNA标签测序进行检测分析。

讨论
本项严谨的临床试验将为针灸作为轻度阿尔茨海默病辅助治疗手段的疗效提供高质量证据，并有望从肠道菌群角度阐明针灸发挥作用的潜在机制。

临床试验注册
[https://clinicaltrials.gov/ct2/show/NCT05078944]，ClinicalTrials.gov 编号[NCT05078944]。该试验于2021年10月15日完成注册。