Effects of baclofen on the functional anatomy of the oesophago-gastric junction and proximal stomach in healthy volunteers and patients with GERD assessed by magnetic resonance imaging and high-resolution manometry: a randomised controlled double-blind st

Abstract

Summary Background The mechanism of reflux protection may involve a ‘flap valve’ at the oesophago‐gastric junction (OGJ). Aim To assess the effects of baclofen, a gamma‐aminobutyric acid receptor type‐B (GABA‐B) agonist known to suppress reflux events, on the ‘functional anatomy’ of the OGJ and proximal stomach after a large test meal. Methods Twelve healthy volunteers (HVs) and 12 patients with gastro‐oesophageal reflux disease (GERD); with erosive oesophagitis or pathological oesophageal acid exposure completed a randomised, double‐blind, cross‐over study. On 2 test days participants received 40‐mg baclofen or placebo before ingestion of a large test meal. OGJ structure and function were assessed by high‐resolution manometry (HRM) and magnetic resonance imaging (MRI) using validated methods. Measurements of the oesophago‐gastric angle were derived from three‐dimensional models reconstructed from anatomic MRI images. Cine‐MRI and HRM identified postprandial reflux events. Mixed model analysis and Wilcoxon rank signed tests assessed differences between participant groups and treatment conditions. Results In both HVs and GERD patients, baclofen reduced the frequency of postprandial reflux events. The oesophago‐gastric insertion angle in GERD patients was reduced (−4.1 ± 1.8, P = 0.025), but was unchanged in healthy controls. In both study groups, baclofen augmented lower oesophageal sphincter (LES) pressure (HVs: +7.3 ± 1.8 mmHg, P < 0.0001, GERD: +4.50 ± 1.49 mmHg, P < 0.003) and increased LES length (HVs: +0.48 ± 0.11 cm, P < 0.0003, GERD: +0.35 ± 0.06 cm, P < 0.0001). Conclusions Baclofen inhibits transient LES relaxations and augments LES pressure and length. Additionally, baclofen has effects on the ‘functional anatomy’ of the OGJ and proximal stomach in GERD patients, which may suppress reflux by means of a ‘flap valve’ mechanism.

Editorial: baclofen and transient lower oesophageal sphincter relaxations – the band plays on ‐ authors' reply

“…[4][5][6] A nationwide French study now published reports on 36 patients with olmesartan-associated enteropathy. 7 This important study further supports the association between olmesartan and sprue-like enteropathy. Interestingly, this report also includes four patients with severe diarrhoea and normal villi, which suggests a spectrum of histological damage.…”

“…4 In the current study the effects of baclofen, a medication known to suppress TLOSRs, 5,6 on OGJ structure and function was assessed in a randomised, placebo-controlled trial. 7 The primary outcome was that the insertion angle was reduced towards normal levels by baclofen in reflux patients. In addition intra-abdominal LOS pressure was increased.…”

Nonerosive reflux disease: clinical concepts

“…Alginates cover the acid pocket and reduce esophageal contact exposure—safety profile is excellent and these may serve a complementary role for some patients . Baclofen, a gamma amino butyric acid B receptor agonist, has been shown to reduce TLESRs and reflux episodes; however, efficacy is limited due to adverse effects and tachyphylaxis . Prokinetics increase gastric emptying and esophageal contraction and may have modest efficacy in some patients; however, limited benefit must be weighed against medical tolerability and risk .…”

The Role of the Acid Pocket in Gastroesophageal Reflux Disease

“…61 A further study confirmed these findings by showing reduced postprandial acid reflux events in both healthy volunteers and GERD patients by inhibiting TLESRs and increasing LES tone. 62 …”