Acosta Andres, Camilleri Michael, Busciglio Irene, Boldingh Amy, Nelson Alfred D, Burton Duane
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN, 55905, USA.
Dig Dis Sci. 2016 Mar;61(3):852-60. doi: 10.1007/s10620-015-3876-5. Epub 2015 Oct 14.
The pentapeptide ghrelin agonist, relamorelin, accelerates colonic transit in patients with chronic constipation (CC). In a murine model, relamorelin decreased excitability of colonic circular smooth muscle cells and colonic intraluminal pressure.
To determine short-term effects of relamorelin on colonic motility measured by barostat and multilumen manometry in CC.
In a placebo-controlled, single-dose, double-blind, randomized study in patients with CC, we investigated the motor effects of relamorelin, 100 μg, SQ (12 patients) compared to placebo SQ (six patients). A motility-barostat balloon assembly was used to measure colonic compliance; tone and phasic pressure activity were measured before and after a 1000-kcal milkshake meal (administered ~60 min post-medication). Overall "background" phasic pressure activity was assessed by: average amplitude and motility index (MI = ln[sum amplitudes × #contractions + 1]) over defined periods. High-amplitude propagating contractions (HAPCs) were characterized by amplitude >75 mmHg and propagating contractions >50 mmHg; both were propagated over at least 10 cm. Postprandial HAPCs were the primary end point. The study sample had 80% power to detect an increase of 3.3 HAPCs in the hour post-meal.
Relamorelin, 100 μg, significantly induced more pre-meal propagated contractions [PCs of either >50 or >75 mmHg] compared to placebo (p < 0.05). Relamorelin also induced more post-meal PCs >50 or >75 mmHg than placebo. Relamorelin did not significantly alter colonic compliance, fasting or postprandial phasic pressure activity (20 min pre-meal fasting MI) or tone, and 60 min postprandial phasic pressure amplitude or MI, or tone.
Relamorelin stimulates propagated colonic contractions without alteration of background irregular contractions in CC. ClinicalTrial.Gov registration number: NCT 01781104.
五肽胃饥饿素激动剂瑞莫瑞林可加速慢性便秘（CC）患者的结肠转运。在小鼠模型中，瑞莫瑞林可降低结肠环形平滑肌细胞的兴奋性和结肠腔内压力。
通过压力传感器和多腔测压法确定瑞莫瑞林对CC患者结肠动力的短期影响。
在一项针对CC患者的安慰剂对照、单剂量、双盲、随机研究中，我们调查了100μg皮下注射瑞莫瑞林（12例患者）与皮下注射安慰剂（6例患者）的运动效应。使用动力压力传感器球囊组件测量结肠顺应性；在摄入1000千卡奶昔餐（给药后约60分钟）前后测量张力和相性压力活动。通过在规定时间段内的平均振幅和运动指数（MI = ln[总振幅×收缩次数 + 1]）评估总体“背景”相性压力活动。高振幅传播收缩（HAPC）的特征为振幅>75 mmHg且传播收缩>50 mmHg；两者均传播至少10 cm。餐后HAPC是主要终点。该研究样本有80%的把握度检测到餐后1小时HAPC增加3.3次。
与安慰剂相比，100μg瑞莫瑞林显著诱导更多餐前传播收缩[>50或>75 mmHg的传播收缩]（p < 0.05）。瑞莫瑞林还比安慰剂诱导更多餐后>50或>75 mmHg的传播收缩。瑞莫瑞林未显著改变结肠顺应性、空腹或餐后相性压力活动（餐前20分钟空腹MI）或张力，以及餐后60分钟相性压力振幅或MI，或张力。
瑞莫瑞林刺激CC患者结肠传播性收缩，而不改变背景不规则收缩。ClinicalTrial.Gov注册号：NCT 01781104。
