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

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83 Scopus citations


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. NCT01396213.

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



  • Celiac Disease
  • Gluten
  • Therapeutic
  • Tight Junction

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

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.