Centre for Musculoskeletal Research, The University of Manchester, Northern Care Alliance NHS Foundation Trust.
NIHR Manchester Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Rheumatology (Oxford). 2023 Feb 1;62(2):824-828. doi: 10.1093/rheumatology/keac426.
Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP.
This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3-7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models.
For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°Cs vs 19 558°Cs), but not significantly (P = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P = 0.036). C21 was well tolerated.
Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation.
ClinicalTrials.gov, https://clinicaltrials.gov, NCT04388176.
我们的主要目的是研究单次口服 C21（一种选择性血管紧张素 II 型 2 型受体激动剂）对 SSc 相关雷诺现象（RP）中冷诱导血管收缩的影响。
这是一项 IIa 期、随机、双盲、交叉、单次剂量、安慰剂对照、单中心研究。12 名女性 SSc 患者（中位年龄 58.5 岁，中位 RP 病程 19.0 年）在 4 个时间点就诊：筛选、治疗访视 1 和 2（间隔 3-7 天）和随访。在第一次治疗访视时，患者被随机分为接受单次口服 C21（200mg）或安慰剂治疗，然后在第二次访视时接受相反的治疗。每次治疗后 40 分钟，每位患者接受标准手部冷挑战。主要终点是 15 分钟内每个手指（8 个手指）复温的曲线下面积（AUC）。次要终点包括复温后最大手指温度（MAX）。统计分析采用乘法 ANCOVA 模型进行。
所有 8 个手指的 AUC 复温均高于 C21 治疗后（几何均数 20046°Cs 与 19558°Cs），但差异无统计学意义（P=0.380），MAX（15 分钟时）也较高（几何均数 23.5°C 与 22.5°C；P=0.036）。C21 耐受良好。
尽管试验规模较小，但仍出现了一个信号，表明即使在已确诊的 SSc 患者中，C21 也可能对 RP 有益，值得进一步研究。
ClinicalTrials.gov，https://clinicaltrials.gov，NCT04388176。
