Zheng, Ting

Current selection of different treatments for patients with gastroparesis is empiric or based on trial and error, though pyloric distensibility and diameter may predict response to pyloric interventions. High-resolution antropyloroduodenal manometry (HR-ADM) can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions in patients with suspected gastroparesis. HR-ADM shows promise to provide guidance for selection and individualization of treatments such as prokinetic agents or pyloric interventions for patients with gastroparesis based on documented pathophysiology.

LINKED CONTENTThis article is linked to Khanna et al papers. To view these articles, visit https://doi.org/10.1111/apt.17065

SummaryBackgroundTradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV).AimTo evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics.MethodsWe conducted a randomised, double‐blind, placebo‐controlled, single‐centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2.ResultsThe two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV.ConclusionTradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis.Clinic trials registryClinicalTrials.gov #NCT04849559.

AbstractBackgroundRecent studies with functional endoluminal imaging probe (EndoFLIP®) measure physiologic characteristics of the pylorus. EndoFLIP® has the potential to select optimal candidates for gastric peroral endoscopic myotomy (G‐POEM). Normative values of the pylorus using EndoFLIP® have not been established.MethodsTwenty‐four healthy volunteers (20–56 years old; 15 females) underwent unsedated, transoral EndoFLIP® measurements of the pylorus after 8 h of fasting. Measurements of diameter (DM), balloon pressure, and distensibility index (DI) of the pylorus were obtained twice over 5 min at 40, 50, and 60 ml balloon distensions.Key ResultsPyloric DM at 40, 50, and 60 ml balloon distensions were 13.0 ± 2.5, 14.3 ± 1.8, and 17.2 ± 2.0 mm, respectively. DM with 60 ml distension was notably higher than with 40 and 50 ml distensions. Pyloric DI at 40, 50, and 60 ml distensions were 10.9 ± 4.8, 11.3 ± 5.8, and 11.1 ± 4.3 mm2/mm Hg, respectively (p = 0.86). Linear regression and Bland–Altman plots showed similar distribution of the DM and DI during the second minute compared with the full 5‐min measurements at 50 ml distension, as well as between two sequential measurements using 50 ml distension. With 50 ml balloon distension, intraindividual coefficients of variation (COVintra) for DM and DI were 13.8% and 29.6%, respectively, and interindividual COV (COVinter) were 12.6% and 51.3%, respectively. Similar reproducibility was obtained with 40 ml balloon distension.Conclusions and InferencesUnsedated EndoFLIP® can be used to characterize human fasting pyloric diameter and distensibility, with best performance observed with 40 ml and 50 ml distensions and data collection during the second minute. Normative values reported serve as reference values for future studies.