Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota.
Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota.
Clin Gastroenterol Hepatol. 2015 Dec;13(13):2312-9.e1. doi: 10.1016/j.cgh.2015.04.184. Epub 2015 May 19.
BACKGROUND & AIMS: Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation. METHODS: We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 μg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants' mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m(2), with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance. RESULTS: Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache. CONCLUSIONS: Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.
背景与目的：胃饥饿素受体位于结肠。雷拉美脲是一种胃饥饿素受体 1a 的五肽选择性激动剂，具有胃作用，但它在结肠中的作用尚不清楚。我们旨在评估雷拉美脲对慢性便秘患者的排便（BMs）、胃肠道和结肠转运（CT）的影响。
方法：我们对 48 名符合罗马 III 标准且每周自发性排便（SBM）少于 4 次的慢性便秘女性患者进行了一项研究。在一项为期 14 天的随机（1:1）、双盲、平行组、安慰剂对照试验中，在 2 家梅奥诊所的为期 14 天的单盲基线期后，测试雷拉美脲（100μg/d，皮下给药）的效果。参与者的平均年龄为 40.6±1.5 岁，平均体重指数为 25.7±0.6kg/m2，每周 1.7±0.1 次 SBM，基线期大便稠度为 1.2±0.1（布里斯托尔量表）。在基线期，24 名结肠转运小于 2.4（几何中心在 24 小时内）的参与者测量了治疗对转运的影响。在接受雷拉美脲或安慰剂的最后 2 天测量胃排空、小肠转运和 CT。患者从第 1 天到第 28 天每天记录排便情况，以确定排便功能。研究终点为首次 BM 时间、每周 SBM 次数、每周完全 SBM 次数、粪便形态和排便通畅程度。通过协方差分析评估雷拉美脲的效果。
结果：与安慰剂相比，雷拉美脲加速了胃排空半衰期（P=0.027）、小肠转运（P=0.051）和 32 小时（P=0.040）和 48 小时（P=0.017）的 CT。与安慰剂相比，雷拉美脲增加了 SBM 次数（P<0.001），并加速了首次给药后的首次 BM 时间（P=0.004），但不影响粪便形态。与雷拉美脲相关的不良事件包括食欲增加、疲劳和头痛。
结论：与安慰剂相比，雷拉美脲在结肠中起作用，可显著减轻慢性便秘患者的便秘症状并加速 CT。临床试验注册编号：NCT01781104。
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