Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain
Article first published online: 16 MAR 2011
© 2011 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 33, Issue 10, pages 1113–1122, May 2011
How to Cite
Krarup, A. L., Ny, L., Åstrand, M., Bajor, A., Hvid-Jensen, F., Hansen, M. B., Simrén, M., Funch-Jensen, P. and Drewes, A. M. (2011), Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain. Alimentary Pharmacology & Therapeutics, 33: 1113–1122. doi: 10.1111/j.1365-2036.2011.04629.x
- Issue published online: 13 APR 2011
- Article first published online: 16 MAR 2011
- Publication data Submitted 8 December 2010 First decision 10 January 2011 Resubmitted 24 February 2011 Accepted 24 February 2011 EV Pub Online 16 March 2011
Aliment Pharmacol Ther 2011; 33: 1113–1122
Background Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor ‘transient receptor potential vanilloid 1’(TRPV1) are a potential drug class for GERD treatment.
Aim To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain.
Methods Twenty-two healthy men (20–31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat.
Results A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10–38%] and 28%, respectively (CI: 14–43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1–3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0–5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported ‘feeling cold’ and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 ± 0.3 °C and 0.7 ± 0.3 °C, respectively, P < 0.05).
Conclusions AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).