A placebo‐controlled trial of the 5‐HT1A agonist R‐137696 on symptoms,visceral hypersensitivity and on impaired accommodation in functional dyspepsia

Abstract Acute studies suggested a therapeutic benefit for fundus‐relaxing drugs in functional dyspepsia (FD) with visceral hypersensitivity (VH) to gastric distention or impaired accommodation (IA), but long‐term studies are lacking. R‐137696 is a serotonin‐1A (5‐HT_1A) receptor agonist which relaxes the proximal stomach in man. Our aim was to investigate the influence of R‐137696 on symptoms in FD with VH or IA. Randomized, double‐blind, placebo‐controlled, parallel group study of 4 weeks R‐137696 2 mg t.i.d. in FD with VH or IA. Symptoms were assessed using the patient assessment of upper gastrointestinal symptom severity index (PAGI‐SYM) total score and individual symptom subscales. Barostat studies were performed before and after 4 weeks of treatment. Fifty‐three patients (33 VH and 20 IA), 18 men, mean age 40 ± 13 years were recruited. Twenty‐four received placebo and 29 received R‐137696. In VH patients, both placebo and R‐137696 improved total symptom scores, with a tendency for superiority of placebo (?1.12 vs?0.51, P = 0.07). Placebo was superior for the subscales of early satiety, bloating, fullness and discomfort (all P < 0.05). In IA, both placebo and R‐137696 had no significant influence on total or individual symptom scores (?0.08 and ?0.27). In VH, both placebo and R‐137696 increased the discomfort volume, without a statistical difference between both arms (+120 and +164 mL). In IA, both placebo and R‐137696 enhanced accommodation, without a statistical difference between both (+77 and +159 mL). Adverse events were similar for drug and placebo. A 4‐week administration of the fundus‐relaxing 5‐HT_1A agonist R‐137696 failed to significantly improve symptoms, VH or gastric accommodation compared to placebo.