A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia.
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.
Tack
J
J
Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. jan.tack@med.kuleuven.ac.be
Van Den Elzen
B
B
Tytgat
G
G
Wajs
E
E
Van Nueten
L
L
De Ridder
F
F
Boeckxstaens
G
G
D000328:Adult; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D003627:Data Interpretation, Statistical; D003915:Dextromethorphan; D004305:Dose-Response Relationship, Drug; D004415:Dyspepsia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005748:Gastric Fundus / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D013270:Stomach / Q000503:physiopathology
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6