Clinical Sciences Building, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK.
Rheumatology (Oxford). 2014 May;53(5):948-52. doi: 10.1093/rheumatology/ket421. Epub 2014 Jan 31.
Our primary purpose was to evaluate the efficacy of the high-potency α2C-adrenoceptor antagonist ORM-12741 in the attenuation of a cold-induced reduction in finger blood flow and temperature in patients with RP secondary to SSc. Secondary objectives were to assess safety and tolerability.
This was a phase IIa, randomized, double-blind, crossover, single-dose, placebo-controlled, single-centre study. Patients attended five times: initial screening, treatment visits 1-3 (each at least 1 week apart) and 1-2 weeks after the last treatment. At each treatment visit, each subject received a single oral dose of 30 mg or 100 mg of ORM-12741 or placebo. Thirty minutes later the subject underwent a cold challenge. Blood flow to the fingers was assessed by three methods [temperature by probe, laser Doppler imaging (LDI) and infrared thermography] performed before, during and after the cold challenge.
Twelve patients (10 female, mean age 58 years) were included. The area under the rewarming curve (LDI) of the right index finger (arbitrary flux units × time) was lower for both 30 mg (P = 0.043) and 100 mg (P = 0.025) of ORM-12741 compared with placebo, indicating delayed reperfusion. The time to 70% temperature recovery (middle finger probe) was longer with active than placebo treatment: mean (s.d.) values for placebo, 30 mg of ORM-12741 and 100 mg of ORM-12741 were 21.4 min (12.4), 25.7 min (12.2) and 26.9 min (13.9), respectively. Overall ORM-12741 was well tolerated.
ORM-12741 did not expedite recovery from a cold challenge in the fingers of patients with SSc.
https://www.clinicaltrialsregister.eu/; no. 2010-024005-13.
我们的主要目的是评估高选择性α2C-肾上腺素受体拮抗剂 ORM-12741 对继发于 SSc 的 RP 患者手指血流和温度受冷诱导降低的缓解作用。次要目的是评估安全性和耐受性。
这是一项 IIa 期、随机、双盲、交叉、单次、安慰剂对照、单中心研究。患者共就诊 5 次：初次筛选、治疗访视 1-3 次（每次至少间隔 1 周）以及末次治疗后 1-2 周。每次治疗访视时，每位受试者接受单次口服 30mg 或 100mg ORM-12741 或安慰剂。30 分钟后，受试者接受冷挑战。手指血流通过三种方法[探头温度、激光多普勒成像（LDI）和红外热成像]在冷挑战前、期间和之后进行评估。
共纳入 12 名患者（10 名女性，平均年龄 58 岁）。与安慰剂相比，右食指的再灌注曲线（LDI）下面积（任意通量单位×时间）在 30mg（P=0.043）和 100mg（P=0.025）的 ORM-12741 时均较低，表明再灌注延迟。与安慰剂相比，活性药物治疗时达到 70%温度恢复（中指探头）的时间更长：安慰剂、30mg ORM-12741 和 100mg ORM-12741 的中位（标准差）值分别为 21.4 分钟（12.4）、25.7 分钟（12.2）和 26.9 分钟（13.9）。总体而言，ORM-12741 具有良好的耐受性。
ORM-12741 并未加速 SSc 患者手指从冷挑战中恢复。
https://www.clinicaltrialsregister.eu/；编号 2010-024005-13。
