Acotiamide affects antral motility, but has no effect on fundic motility, gastric emptying or symptom perception in healthy participants

Abstract

Background Acotiamide, a prokinetic agent was shown to be efficacious in the treatment of functional dyspepsia (FD). The exact mechanism of action is incompletely elucidated. Methods This randomized, placebo‐controlled, cross‐over study aimed to examine the effect of acotiamide on gastric motility, measured as intragastric pressure, gastric emptying (GE) rate and gastrointestinal (GI) symptom perception in healthy volunteers (HVs). Participants were treated with acotiamide (100 mg tid) and placebo for 3 weeks, separated by a 1‐week washout period. A daily symptom diary was collected during both treatments. At the end of each treatment period, GE rate and gastric motility were assessed with a 13C‐octanoic acid breath test and high‐resolution manometry during nutrient infusion, respectively. GI symptom levels were scored during high‐resolution manometry. Data were analyzed using mixed models. The study was registered as NCT03402984. Key Results Twenty HVs (10 female, 25 ± 4.1 years, 22.58 ± 2.73 kg/m2) participated in the study. There was no difference in GE half time between both treatments (P = 0.92). Acotiamide had no effect on fundic pressures before and after nutrient infusion (P = 0.91). However, postprandial antral pressures remained significantly lower compared to placebo (P = 0.015). There was no significant difference in hunger, satiation and GI symptoms scores assessed during IGP measurement and by the daily diary (P > 0.12 for all). Conclusion Acotiamide is associated with lower antral pressures after nutrient intake, whereas it has no effect on fundic pressures, GE rate and symptom perceptions in HVs. Studies in FD need to elucidate whether lower antral pressures induced by acotiamide underlie postprandial symptom improvement in FD.

Early effects of acotiamide or mosapride intake on gastric emptying: a randomized 3-way crossover study using the ¹³C breath test

“…The finding that acotiamide had no effect on the gastric emptying rate is consistent with the results reported by Zai et al (5) and Masuy et al (7) The effects of commonly used drugs on gastric emptying in patients with functional gastrointestinal disease are summarized in Table 2. (5)(6)(7)(15)(16)(17)(18)(19)(20) In clinical settings, various drugs are used to treat dyspepsia in patients with functional gastrointestinal disease, but few drugs improve gastric emptying. Proton pump inhibitors, which are frequently used to treat dyspepsia in patients with functional gastrointestinal disease, delay gastric emptying.…”

“…The reported effects of acotiamide on gastrointestinal function are summarized in Table 3. (5)(6)(7)(25)(26)(27) Many reports indicate that acotiamide has no effect on gastrointestinal function. Current trackable gastrointestinal function tests may not be able to detect changes in gastrointestinal function caused by acotiamide.…”

“…Masuy et al (7) → (HV) Nakamura et al (6) ↑ (FD) Kusunoki et al (21) ↑ (HV) Sakamoto et al (15) ↑ (HV) Kusunoki et al (16) ↑ (FD) Nonaka et al (17) → (HV/FD) Abid et al (18) → (FD)…”

“…The effect of acotiamide on gastric emptying varies from report to report, as there are reports that there is no effect on gastric emptying and reports that it promotes gastric emptying. (5)(6)(7) The gastrointestinal motility effects of acotiamide have not yet been sufficiently investigated. The aim of this study was to determine whether single preprandial acotiamide intake might have an effect on the rate of liquid gastric emptying using the 13 C breath test.…”

Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders

“…Acotiamide [ClinicalTrials.gov: NCT03402984 (phase 2)], a muscarinic receptor antagonist (acetylcholinesterase inhibitor), antagonizes the presynaptic muscarinic receptors and has a prokinetic effect throughout the gut ( Altan et al, 2012 ; Masuy et al, 2019a ) and has been developed and approved in Japan and India for the treatment of FD. Studies have shown its efficacy in improving impaired gastric accommodation in patients with FD ( Altan et al, 2012 ; Matsueda et al, 2012 ).…”