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Gastroenterology. 2015 Jun;148(7):1311-9.e6. doi: 10.1053/j.gastro.2015.02.008. Epub 2015 Feb 13.

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

Author information

1
The Celiac Center at Beth Israel Deaconess Medical Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
2
Celiac Disease Center at Columbia University, New York, New York.
3
Center of Excellence for Gastrointestinal Immunity and Inflammation Research, University of Alberta, Edmonton, Alberta, Canada.
4
Thomas Jefferson University, Philadelphia, Pennsylvania.
5
Alba Therapeutics Corporation, Baltimore, Maryland.
6
McMaster University, Hamilton, Ontario, Canada.
7
Essentia Health Duluth Clinic, Duluth, Minnesota.
8
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: Murray.joseph@mayo.edu.

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.

KEYWORDS:

Celiac Disease; Gluten; Therapeutic; Tight Junction

PMID:
25683116
PMCID:
PMC4446229
DOI:
10.1053/j.gastro.2015.02.008
[Indexed for MEDLINE]
Free PMC Article

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