Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain
Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain
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DOI：
10.1111/j.1365-2036.2011.04629.x
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发表时间：
2011-05-15
影响因子：
7.6
通讯作者：
Drewes, A. M.
中科院分区：
文献类型：
--
作者：
Krarup, A. L.;Ny, L.;Drewes, A. M.
许多胃食管反流病（GERD）患者对热和酸过敏，标准治疗可能疗效不佳。热酸受体瞬时受体电位香草酸1（TRPV 1）拮抗剂是治疗胃食管反流病（GERD）的潜在药物，目的研究TRPV 1拮抗剂AZD 1386对实验性食管疼痛的影响（20-31岁）参加了这项随机、安慰剂对照、双盲、交叉研究，检查单次口服AZD 1386（30和95 mg）的作用。受试者接受区组随机化。在治疗日，参与者被刺激疼痛的热，膨胀，电流和食管酸。前臂的热痛和压痛是躯体控制刺激。数据分析：意向treat.ResultsA共21名参与者完成了协议和1自愿中止。在食管中，30和95 mg AZD 1386分别使热刺激的痛阈增加23% [95%置信区间（CI）：10-38%]和28%（CI：14-43%）。30 mg AZD 1386后皮肤耐热性增加2.1 ℃（CI：1.1-3.2 ℃），95 mg AZD 1386后增加4.0 ℃（CI：3.0-5.0 ℃）。热镇痛持续2.5h。其他刺激的疼痛阈值不受AZD 1386的影响。在所有暴露于30和95 mg AZD 1386的受试者中，50%的受试者报告“感觉寒冷”和体温升高（分别平均升高0.4 +/- 0.3 ℃和0.7 +/- 0.3 ℃，P < 0.05）。结论AZD 1386增加食管和皮肤热痛阈值，不良事件安全。该类药物可能具有治疗GERD的潜力（ClinicalTrials.gov标识符：NCT 00711048）。
P>BackgroundMany patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment.AimTo investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain.MethodsTwenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat.ResultsA total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 degrees C (CI: 1.1-3.2 degrees C) after 30 mg AZD1386 and 4.0 degrees C (CI: 3.0-5.0 degrees C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 +/- 0.3 degrees C and 0.7 +/- 0.3 degrees C, respectively, P < 0.05).ConclusionsAZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).