An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis – A proof of concept trial

ObjectivesThe primary objective of this trial was to assess safety and anti-inflammatory effects of an add-on training program involving breathing exercises, cold exposure, and meditation in patients with axial spondyloarthritisMethodsThis study was an open-label, randomised, one-way crossover clinical proof-of-concept trial. Twenty-four patients with moderately active axial spondyloarthritis(ASDAS >2.1) and hs-CRP ≥5mg/L were included and randomised to an intervention (n = 13) and control group (n = 11) group that additionally received the intervention after the control period. The intervention period lasted for 8 weeks. The primary endpoint was safety, secondary endpoints were change in hs-CRP, serum calprotectin levels and ESR over the 8-week period. Exploratory endpoints included disease activity measured by ASDAS-CRP and BASDAI, quality of life (SF-36, EQ-5D, EQ-5D VAS), and hospital anxiety and depression (HADS).ResultsWe found no significant differences in adverse events between groups, with one serious adverse event occurring 8 weeks after end of the intervention and judged ‘unrelated’. During the 8-week intervention period, there was a significant decline of ESR from (median [interquartile range] to 16 [9–26.5] to 9 [5–23] mm/hr, p = 0.040, whereas no effect was found in the control group (from 14 [8.3–27.3] to 16 [5–37] m/hr, p = 0.406). ASDAS-CRP declined from 3.1 [2.5–3.6] to 2.3 [1.9–3.2] in the intervention group (p = 0.044). A similar trend was observed for serum calprotectin (p = 0.064 in the intervention group versus p = 0.182 in the control group), but not for hs-CRP.ConclusionsThis proof-of-concept study in axial spondyloarthritis met its primary endpoint with no safety signals during the intervention. There was a significant decrease in ESR levels and ASDAS-CRP upon the add-on training program in the intervention group. These findings warrant full-scale randomised controlled trials of this novel therapeutic approach in patients with inflammatory conditions.Trial registrationClinicalTrials.gov; NCT02744014

研究目的
本临床试验的核心目标为评估针对中轴型脊柱关节炎（axial spondyloarthritis）患者，附加呼吸训练、冷暴露与冥想的联合训练方案的安全性与抗炎效果。

研究方法
本研究为一项开放标签、随机单向交叉设计的临床概念验证试验。共纳入24例中度活动期中轴型脊柱关节炎（ASDAS>2.1）且高敏C反应蛋白（hs-CRP）≥5mg/L的患者，按13:11的比例随机分为干预组与对照组，对照组在干预周期结束后额外接受该干预方案。干预周期时长为8周。本试验的主要终点为安全性，次要终点为8周干预期间高敏C反应蛋白、血清钙卫蛋白水平与红细胞沉降率（ESR）的变化情况。探索性终点包括通过ASDAS-CRP与BASDAI评估的疾病活动度、生活质量（SF-36、EQ-5D、EQ-5D VAS）以及医院焦虑抑郁量表（HADS）评分。

研究结果
两组患者的不良事件发生率无显著差异，仅1例严重不良事件发生于干预结束后8周，且判定为与研究干预无关。在8周的干预周期内，干预组的红细胞沉降率从基线的中位数[四分位间距]16[9–26.5]mm/hr显著下降至9[5–23]mm/hr（p=0.040），而对照组无明显变化（从14[8.3–27.3]mm/hr降至16[5–37]mm/hr，p=0.406）。干预组的ASDAS-CRP评分从3.1[2.5–3.6]下降至2.3[1.9–3.2]（p=0.044）。血清钙卫蛋白水平呈现类似的下降趋势（干预组p=0.064，对照组p=0.182），但高敏C反应蛋白水平未观察到类似变化。

结论
这项针对中轴型脊柱关节炎的概念验证试验达成了主要终点，干预期间未出现安全性信号。干预组患者在接受该附加训练方案后，红细胞沉降率与ASDAS-CRP评分均出现显著下降。上述研究结果支持针对炎症性疾病患者开展该新型治疗方案的大规模随机对照试验。

试验注册
ClinicalTrials.gov；NCT02744014