Duodenal Rather Than Gastric Motility Parameters Correlate With Symptom Severity in Patients With Diabetic Gastroparesis

Abstract

Introduction: Gastroparesis symptom severity correlates poorly with rate of gastric emptying. Previously, we showed that duodenal contractility correlated better than gastric motility with symptoms (Barshop K, DDW 2014). To confirm these findings, we assessed the correlation of contractility with gastroparesis symptoms in patients taking the investigational motilin agonist camicinal (C) or placebo, using wireless motility capsule (WMC). The design, primary efficacy, and safety results of this study have been previously reported (Barton ME, DDW 2014). Patients receiving C 10 mg or 50 mg showed improvement in symptoms vs. placebo;125 mg did not. Methods: Diabetics with gastroparesis (confirmed by 13 C oral breath test) with at least moderate symptoms were enrolled in a double blind randomized study of placebo, 10, 50, or 125 mg doses of C daily for 28 days. The 3 dosage groups were combined for analyses. Symptom severity assessed by Gastroparesis Cardinal Symptom Index (GCSI) was averaged for the first 7 days of treatment. Gut contractility was assessed on day 1, 90 minutes following the initial dose. The frequency of contractions (CT), area under pressure curve (AUC), and motility index (MI) were analyzed in the 1-hour period prior to (antral [A] window) and post (duodenal [D] window) WMC gastric emptying (GET). Results: Seventy-nine subjects were enrolled. The most common investigator assessed drug-related AEs were headache, UTI, and GI symptoms, generally similar in frequency across treatment groups. There were no study withdrawals due to AEs, nor any drug-related serious AEs. Gut contractility parameters poorly correlated with symptom severity for the treatment cohort (n=51; r<0.14) and placebo cohort (n=10; r<0.26) in either A or D windows. The subgroup of subjects (n=14) with delayed gastric emptying (WMC GET>5 hrs) treated with C showed moderate correlations in the D window between postprandial fullness and CT, AUC, and MI (r= -0.43, -0.51, -0.45; p>0.12). Symptom improvement was observed at the 2 lower doses (10 and 50 mg) of C. Further analysis was conducted with these treatment groups (n=10). Small bowel CT correlated moderately with GCSI total score (r= -0.76; p=0.01), bloating (r= -0.72; p=0.02), and postprandial fullness (r= -0.84; p<0.01). Weak correlations between symptoms and gastric contractility were observed even with the sample limited to gastroparetics and the 125-mg dose group removed. Conclusion: Data suggests duodenal contractile parameters moderately correlated with gastroparesis symptoms in patients with delayed gastric emptying treated with a motilin agonist. The correlation of symptoms with duodenal motility was strongest with doses where patients reported symptomatic improvement. Disclosure - George Dukes - Employee, GSK. Matthew Barton - Employee, GSK. Kenneth Barshop - none. Braden Kuo - Consultant, GSK. Jack Semler - Consultant, GSK, GivenImaging. This research was supported by an industry grant from GlaxoSmithKline(GSK).