title: Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.
abstract: OBJECTIVE
  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.
authors: The Celiac Center at Beth Israel Deaconess Medical Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors: Daniel A
authors: DA
authors: Leffler
authors: The Celiac Center at Beth Israel Deaconess Medical Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors: Ciaran P
authors: CP
authors: Kelly
authors: Celiac Disease Center at Columbia University, New York, New York.
authors: Peter H R
authors: PH
authors: Green
authors: Center of Excellence for Gastrointestinal Immunity and Inflammation Research, University of Alberta, Edmonton, Alberta, Canada.
authors: Richard N
authors: RN
authors: Fedorak
authors: Thomas Jefferson University, Philadelphia, Pennsylvania.
authors: Anthony
authors: A
authors: DiMarino
authors: Alba Therapeutics Corporation, Baltimore, Maryland.
authors: Wendy
authors: W
authors: Perrow
authors: Alba Therapeutics Corporation, Baltimore, Maryland.
authors: Henrik
authors: H
authors: Rasmussen
authors: Alba Therapeutics Corporation, Baltimore, Maryland.
authors: Chao
authors: C
authors: Wang
authors: McMaster University, Hamilton, Ontario, Canada.
authors: Premysl
authors: P
authors: Bercik
authors: Essentia Health Duluth Clinic, Duluth, Minnesota.
authors: Natalie M
authors: NM
authors: Bachir
authors: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: Murray.joseph@mayo.edu.
authors: Joseph A
authors: JA
authors: Murray
mesh_terms: D000328:Adult; D002446:Celiac Disease / Q000150:complications / Q000175:diagnosis / Q000178:diet therapy* / Q000188:drug therapy*; D003131:Combined Modality Therapy; D055050:Diet, Gluten-Free; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D009842:Oligopeptides; C525167:larazotide acetate
keywords: Celiac Disease; Gluten; Therapeutic; Tight Junction