Original ResearchFull Report: Clinical—Alimentary TractGlutenase ALV003 Attenuates Gluten-Induced Mucosal Injury in Patients With Celiac Disease
Section snippets
Gluten-Dose Optimization
To determine the optimal dose of gluten to be used in the interventional study, gluten challenges with 1.5 g, 3.0 g, or 6.0 g gluten (using breadcrumbs) were administered daily to adult celiac disease patients for 6 weeks (see Supplementary Material for gluten content assessment). Eligibility criteria included celiac disease diagnosis established by duodenal mucosal biopsy, attempted adherence to a GFD for 1 year or more, and being in clinical remission (ie, TG2-IgA−negative and reporting
Gluten-Dose Optimization
Before conducting the therapeutic intervention study, the optimal gluten-challenge dose was identified. Forty-seven patients were enrolled (Table 1) and assigned to 1 of 3 groups receiving a gluten challenge of 6.0 g (n = 17), 3.0 g (n = 15), or 1.5 g (n = 15) daily divided in 3 doses. The baseline mean VH:CrD values were similar in each group: 2.8, 2.6, and 2.8, respectively. All patients in the 6 g gluten/day group completed the study; 2 patients in the 3.0 g/day and 1 in the 1.5 g/day gluten
Discussion
Many celiac disease patients desire a novel nondietary alternative to the strict life-long GFD.14, 15, 35, 36 Despite long-term dietary gluten exclusion, small intestinal mucosal injury with crypt hyperplasia (Marsh grade II−III) is still present in 20%−80% of patients.12 In Finland, despite villus recovery in response to the GFD (96% with Marsh grade 0−I), persistent intraepithelial lymphocytosis is seen in more than half of patients studied.12 Small bowel mucosal healing is a prerequisite for
Acknowledgments
The authors are grateful to Robert N. Williams for the assistance with graphics design and statistical support.
Clinicaltrial.gov, ID: NCT00959114 and NCT01255696.
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Conflicts of interest These authors disclose the following: Marja-Leena Lähdeaho is the principal investigator and is employed by FinnMedi Oy. Tiina Kärjä-Lahdensuu is an employee of FinnMedi Oy. Annette Marcantonio and Daniel C. Adelman are employees of Alvine Pharmaceuticals, Inc. Markku Mäki is a scientific advisor to Alvine Pharmaceuticals, Inc., ImmusanT, Inc, BioLineRx, Ltd, and Flamentera, AG. The remaining authors disclose no conflicts.
Funding This study was sponsored by Alvine Pharmaceuticals, Inc., San Carlos, CA. Celiac Disease Study Group (M.-L.L., K.K., K.L., and M.M.) received financial supported by the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (Grants 9R034 and 9R018), Academy of Finland, and The Sigrid Juselius Foundation.