Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: A randomized controlled trial

Daniel A. Leffler, Ciaran P. Kelly, Peter H.R. Green, Richard N. Fedorak, Anthony Dimarino, Wendy Perrow, Henrik Rasmussen, Chao Wang, Premysl Bercik, Natalie M. Bachir, Joseph A. Murray

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P =.022; mixed model for repeated measures, P =.005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days (P =.017), a 31% increase in improved symptom days (P =.034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment (P =.022), and a decrease in the nongastrointestinal symptoms of headache and tiredness (P =.010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213.

Original languageEnglish (US)
Pages (from-to)1311-1319.e6
JournalGastroenterology
Volume148
Issue number7
DOIs
StatePublished - Jun 1 2015

Keywords

  • Celiac Disease
  • Gluten
  • Therapeutic
  • Tight Junction

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Leffler, D. A., Kelly, C. P., Green, P. H. R., Fedorak, R. N., Dimarino, A., Perrow, W., Rasmussen, H., Wang, C., Bercik, P., Bachir, N. M., & Murray, J. A. (2015). Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: A randomized controlled trial. Gastroenterology, 148(7), 1311-1319.e6. https://doi.org/10.1053/j.gastro.2015.02.008