Premium
Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain
Author(s) -
Krarup A. L.,
Ny L.,
Åstrand M.,
Bajor A.,
HvidJensen F.,
Hansen M. B.,
Simrén M.,
FunchJensen P.,
Drewes A. M.
Publication year - 2011
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2011.04629.x
Subject(s) - medicine , placebo , crossover study , gerd , gastroenterology , antagonist , trpv1 , confidence interval , anesthesia , reflux , transient receptor potential channel , disease , receptor , pathology , alternative medicine
Aliment Pharmacol Ther 2011; 33: 1113–1122 Summary 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).