Patients with celiac disease experienced less-severe gastrointestinal symptom escalation following a gluten challenge while taking low doses of larazotide acetate in a recent study.
In a multicenter, dose-ranging study, 86 patients randomly received placebo or 0.25 mg, 1 mg, 4 mg or 8 mg larazotide acetate three times daily, with or without a 2.4 g/day gluten challenge, for 14 days. All participants had biopsy-confirmed celiac disease in remission and had been on a gluten-free diet for 6 months or longer before enrollment. Urinary lactulose/mannitol (LAMA) fractional excretion ratio was established for each patient, as were severity of gastrointestinal symptoms and quality of life.
Investigators did not find a significant difference in LAMA ratio increase between the challenge and nonchallenge groups, although the increase was greater in the treated group. In the challenge group, no significant ratio difference was observed between the treated groups and the placebo group that undertook gluten challenge. Ratios varied widely within all groups, which researchers suggested was due to the outpatient trial setting.
Treated patients experienced less-severe increases in GI symptoms following the challenge than untreated patients, but the difference was only found statistically significant in the 0.25 mg- and 4.0 mg-dose groups (P=.009 for 0.25 mg, P=.067 for 1 mg, P=.025 for 4 mg and P=.329 for 8 mg). Treated patients also were less likely to exhibit signs of gluten toxicity (50.0% of challenged patients receiving placebo vs. 20.8% of treated patients, P=.046).
Daniel A. Leffler
“This is the first clinical trial published on a drug for celiac disease,” Daniel A. Leffler, MD, MS, director of clinical research at the Celiac Center at Beth Israel Deaconess Medical Center in Boston, told Healio.com. “This is also the first trial with a new class of small molecule drugs aimed primarily at affecting the tight junctions between intestinal epithelial cells. … Novel adjunctive therapies to the gluten-free diet are under development and, if found to be efficacious, should be available in the coming years.”
Disclosure: See the study for a full list of relevant disclosures.