Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST)

Abstract

Background: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT₁ receptor agonist, may improve fundic accommodation.

Aim: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis.

Methods: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values.

Results and conclusions: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, p_TX*GROUP = 0.003; p_BF = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo.

Conclusions: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating.

Trial registration: ClinicalTrials.gov NCT0358714285.

Figure 1.. CONSORT Patient Flow for BESST trial.

Of 131 patients assessed for eligibility, 96 patients were randomised; 47 to buspirone, and 49 to placebo.

Figure 2.. Changes from baseline over time for buspirone and placebo treated patients in symptoms measured by the PAGI-SYM. A. ES/PPF Subscore, B. GCSI C. nausea/vomiting subscore, D. bloating subscore, E. upper abdominal pain subscore, and F. Gastroesophageal Reflux Disease subscore.

Description: Graphs plotting the time course of adjusted mean change from baseline for each outcome score at each visit and two-sided 95% confidence intervals by treatment group across visit (screening, 2, 4, 6 weeks) are presented. The significance of the overall treatment effect of change over time was computed from generalized estimating equations (GEE) linear regression, modeling change as a function of treatment group, visit code indicator, baseline value of the outcome, and a treatment group by visit code interaction term. The P’s are reported for the trend from baseline to end-of treatment at week 4. Results for buspirone are plotted in blue solid lines, and for placebo in black dashed lines. Number of patients at visit 0, 2, 4, 6, respectively, are: Buspirone: 47, 39, 39, 33; Placebo: 49, 43, 39, 38.

Figure 3.. Subgroup variation in the 4-week change from baseline in early satiety/postprandial fullness subscore between treatment groups using prespecified baseline post-randomization subgroups

Subgroups displayed are: 1) Etiology: Diabetic vs Idiopathic, 2) Bloating: Severe/very severe vs none to moderate, 3) Water Load Satiety Test volume consumed: Low vs Normal, 4) Narcotic use 3+ times/week or less: No use vs used.