Celiac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet, which is difficult for many patients.
Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae.
Dr Kelly and colleagues from Massachussetts, USA evaluated the efficacy and tolerability of larazotide acetate during gluten challenge.
The research team performed an exploratory, double-blind, randomized, placebo-controlled study including 184 patients who maintained a gluten-free diet before and during the study.
After a gluten-free diet run-in, patients were randomized to larazotide acetate or placebo, and received 2.7 grams of gluten daily for 6 weeks.
|Larazotide acetate 1-mg limited gluten-induced symptoms |
|Alimentary Pharmacology & Therapeutics|
The researchers' outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale, and anti-transglutaminase antibody levels.
The research team observed no significant differences in lactulose-to-mannitol ratios between larazotide acetate and placebo groups.
Larazotide acetate 1-mg limited gluten-induced symptoms measured by Gastrointestinal Symptom Rating Scale.
Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19 in the placebo group compared with 6, 4 and 8 in the larazotide acetate 1-, 4-, and 8-mg groups, respectively.
The team found that the adverse event rates were similar between larazotide acetate and placebo groups.
Dr Kelly and colleagues commented, "Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with celiac disease undergoing gluten challenge and was generally well tolerated."
"However, no significant difference in lactulose-to-mannitol ratios between larazotide acetate and placebo was observed."
"Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with celiac disease."