Abstract：
BACKGROUND: Chronic fatigue syndrome (CFS) severely impact patients\' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS.
OBJECTIVE: To evaluate the efficacy and safety of SJZD for CFS.
METHODS: A multi-center, double-blinded, randomized controlled trial.
METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect.
RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study.
CONCLUSIONS: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD\'s application.
BACKGROUND: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).
OBJECTIVE: To evaluate the efficacy and safety of SJZD for CFS.
METHODS: A multi-center, double-blinded, randomized controlled trial.
METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect.
RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study.
CONCLUSIONS: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD\'s application.
BACKGROUND: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).
摘要：
背景：慢性疲劳综合征（CFS）严重影响患者的生活质量，缺乏公认的药物治疗。四君子汤（SJZD），经典的中草药配方，在中国已广泛用于脾虚证如疲劳。然而,目前尚缺乏SJZD治疗CFS疗效的证据.
目的：评价SJZD治疗CFS的有效性和安全性。
方法：多中心，双盲,随机对照试验。
方法：明确诊断为CFS和脾虚综合征的参与者以1：1的比例随机分配接受SJZD或安慰剂颗粒治疗2个月。主要结局是治疗后Chalder疲劳问卷（CFQ）评分的变化。其他结果包括短表36身体功能（SF36-PF）评分的变化，脾虚量表评分,Euroqol问卷-视觉模拟量表(ED-VAS)评分,并通过相应的问卷对临床总体印象(CGI)进行评估。进行粪便宏基因组测序以探索SJZD效应的潜在机制。
结果：从2020年6月到2021年7月，127名参与者中有105名在中国四家医院完成了研究。经过2个月的治疗，意向治疗（ITT）分析发现，接受SJZD的参与者比安慰剂对照组的减少更大（平均变化6.65[标准差（SD）6.11]点与5.31[SD5.19]点；差异1.34，95%置信区间[CI]-0.65至3.33）。按照方案（PP）分析报告了SJZD组和安慰剂组之间的确认结果（2.24，95％CI0.10至4.39）。与安慰剂相比，SJZD在每个方案人群中也显着改善了整体健康状况（p=0.009）。各组间SF36-PF的变化无显著性差异,脾虚量表评分,CGI。粪便宏基因组测序和相关性分析表明，SJZD的有益作用可能与乳酸片球菌的丰度变化有关。在整个研究过程中没有发现严重的不良事件或异常的实验室检查。
结论：我们的结果表明，在良好的服药依从性下，SJZD可以改善CFS患者的疲劳症状和总体健康状况。潜在的治疗效果可能与肠道微生物群的调节有关。鼓励干预期较长的大规模试验，以进一步支持SJZD的应用。
背景：（ID，ISRCTN23930966，URL=https://www。isrctn.com/ISRCTN23930966).
目的：评价SJZD治疗CFS的有效性和安全性。
方法：多中心，双盲,随机对照试验。
方法：明确诊断为CFS和脾虚综合征的参与者以1：1的比例随机分配接受SJZD或安慰剂颗粒治疗2个月。主要结局是治疗后Chalder疲劳问卷（CFQ）评分的变化。其他结果包括短表36身体功能（SF36-PF）评分的变化，脾虚量表评分,Euroqol问卷-视觉模拟量表(ED-VAS)评分,并通过相应的问卷对临床总体印象(CGI)进行评估。进行粪便宏基因组测序以探索SJZD效应的潜在机制。
结果：从2020年6月到2021年7月，127名参与者中有105名在中国四家医院完成了研究。经过2个月的治疗，意向治疗（ITT）分析发现，接受SJZD的参与者比安慰剂对照组的减少更大（平均变化6.65[标准差（SD）6.11]点与5.31[SD5.19]点；差异1.34，95%置信区间[CI]-0.65至3.33）。按照方案（PP）分析报告了SJZD组和安慰剂组之间的确认结果（2.24，95％CI0.10至4.39）。与安慰剂相比，SJZD在每个方案人群中也显着改善了整体健康状况（p=0.009）。各组间SF36-PF的变化无显著性差异,脾虚量表评分,CGI。粪便宏基因组测序和相关性分析表明，SJZD的有益作用可能与乳酸片球菌的丰度变化有关。在整个研究过程中没有发现严重的不良事件或异常的实验室检查。
结论：我们的结果表明，在良好的服药依从性下，SJZD可以改善CFS患者的疲劳症状和总体健康状况。潜在的治疗效果可能与肠道微生物群的调节有关。鼓励干预期较长的大规模试验，以进一步支持SJZD的应用。
背景：（ID，ISRCTN23930966，URL=https://www。isrctn.com/ISRCTN23930966).
