Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study. METHODS: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately. RESULTS: 202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081). CONCLUSIONS: Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS. TRIAL REGISTRATION NUMBER: The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).

Efficacy of treatment for patients with achalasia depends on the distensibility of the esophagogastric junction.

BACKGROUND & AIMS: Many patients with persistent dysphagia and regurgitation after therapy have low or no lower esophageal sphincter (LES) pressure. Distensibility of the esophagogastric junction (EGJ) largely determines esophageal emptying. We investigated whether assessment of the distensibility of the EGJ is a better and more integrated parameter than LES pressure for determining efficacy of treatment for patients with achalasia. METHODS: We measured distensibility of the EGJ using an endoscopic functional luminal imaging probe (EndoFLIP) in 15 healthy volunteers (controls; 8 male; age, 40 ± 4.1 years) and 30 patients with achalasia (16 male; age, 51 ± 3.1 years). Patients were also assessed by esophageal manometry and a timed barium esophagogram. Symptom scores were assessed using the Eckardt score, with a score <4 indicating treatment success. The effect of initial and additional treatment on distensibility and symptoms was evaluated in 7 and 5 patients, respectively. RESULTS: EGJ distensibility was significantly reduced in untreated patients with achalasia compared with controls (0.7 ± 0.9 vs 6.3 ± 0.7 mm(2)/mm Hg; P < .001). In patients with achalasia, EGJ distensibility correlated with esophageal emptying (r = -0.72; P < .01) and symptoms (r = 0.61; P < .01) and was significantly increased with treatment. EGJ distensibility was significantly higher in patients successfully treated (Eckardt score <3) compared with those with an Eckardt score >3 (1.6 ± 0.3 vs 4.4 ± 0.5 mm(2)/mm Hg; P = .001). Even when LES pressure was low, EGJ distensibility could be reduced, which was associated with impaired emptying and recurrent symptoms. CONCLUSIONS: EGJ distensibility is impaired in patients with achalasia and, in contrast to LES pressure, is associated with esophageal emptying and clinical response. Assessment of EGJ distensibility by EndoFLIP is a better parameter than LES pressure for evaluating efficacy of treatment for achalasia.