Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers.

BACKGROUND: Synthetic human ghrelin accelerates gastric emptying, reduces gastric accommodation, and results in numerical increases in postprandial symptom scores. The ghrelin receptor agonist, relamorelin, accelerates gastric emptying in patients with diabetic gastroparesis. AIM: To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers. METHODS: In a placebo-controlled, double-blind, randomized study of 16 healthy volunteers, we compared effects of 30 µg subcutaneous (s.c.) relamorelin to placebo on: (i) gastric volumes measured by single photon emission computed tomography, (ii) 1-h postprandial distal antral motility index (MI) by 15-lumen perfusion gastroduodenal manometry, and (iii) satiation tested by Ensure nutrient drink test. Primary endpoints were: fasting and postprandial gastric volumes, distal antral phasic pressure activity (number of contractions, mean amplitude, and MI), and maximum tolerated volume. Results were normally distributed and the two treatment groups were compared using t-test. KEY RESULTS: Relamorelin, 30 µg s.c., significantly increased the number of contractions in the distal antrum during 0-60 min postmeal when compared to placebo (p = 0.022); this was also observed in the first two 15-min periods (p = 0.005 and 0.015 for number of contractions 0-15 and 16-30). There was borderline increase in MI0-15 (p = 0.055) and numerically increased MI0-60 (p = 0.139) and MI16-30 (p = 0.116). The amplitude of contractions was not significantly increased. Relamorelin did not significantly alter fasting or postprandial gastric volumes, gastric accommodation, or satiation volumes and symptoms. CONCLUSIONS & INFERENCES: Relamorelin increases frequency of distal antral motility contractions without significant effects on amplitude of contractions. The lack of inhibition of accommodation and absence of increase in satiation symptoms support relamorelin for the treatment of symptomatic gastroparesis (ClinicalTrials.gov NCT02466711).

Randomised clinical trial: the effects of daikenchuto, TU-100, on gastrointestinal and colonic transit, anorectal and bowel function in female patients with functional constipation.

BACKGROUND: Daikenchuto, a Japanese herbal medicine used for post-operative ileus and constipation, dose dependently stimulates gastrointestinal (GI) motility and decreases rectal compliance and sensation. Effects of TU-100 (commercial form of daikenchuto) in adults with constipation are unknown. AIM: To compare the effects of oral TU-100, 2.5 g t.d.s. or 5 g t.d.s. and placebo t.d.s. on GI and colonic transit (CT), rectal compliance (RC) and sensation thresholds (RST), anal sphincter pressures (ASP) and bowel function in female patients with functional constipation (FC). METHODS: We conducted a single-centre, randomised, parallel-group, double-blind, pharmacodynamic study; 45 female patients with FC without evidence of rectal evacuation disorder were assigned to 28 days' treatment with oral placebo or TU-100 (Tsumura USA, Princeton, NJ, USA). Demographic data and CT were measured at baseline and randomisation stratified by baseline CT (GC> or <1.9) and by BMI (<25 or ≥25 kg/m(2) ). At the end of treatment period, we measured GI and CT by scintigraphy, RST and RC by barostat, ASP by manometry, psychosensory sensations, bowel function by daily diary and quality of life (QOL). The study had power to detect effect sizes of 33% (CT), 40% (RC) and 46% (RST). Statistical analysis included BMI as covariate. RESULTS: TU-100 had no significant effects on GI or CT, RC, ASP, recto-anal pressure difference, or RST. The 5 g t.d.s./day dose was associated with lower RST for first sensation and gas (unadjusted P: 0.045 and 0.024 respectively). There were no treatment effects on psychosensory symptoms, stool frequency, stool consistency or QOL. CONCLUSION: Mechanisms underlying the observed clinical benefit of TU-100 remain unclear (ClinicalTrials.gov NCT01139216).