Effect of amiloride on experimental acid-induced heartburn in non-erosive reflux disease

Dig Dis Sci. 2013 Jul;58(7):1955-9. doi: 10.1007/s10620-013-2586-0. Epub 2013 May 7.

Abstract

Background: Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion.

Methods: In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent.

Results: 14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05).

Conclusions: Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channel Blockers / therapeutic use*
  • Administration, Topical
  • Adolescent
  • Adult
  • Aged
  • Amiloride / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Gastroesophageal Reflux / complications*
  • Heartburn / drug therapy*
  • Heartburn / etiology
  • Humans
  • Hydrochloric Acid / administration & dosage
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Acid Sensing Ion Channel Blockers
  • Amiloride
  • Hydrochloric Acid