Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

• DOI: 10.2337/dc21-0318
• Publication Date: 2021-05-21T15:20:16Z
• Authors: Johnny Ludvigsson; Zdenek Sumnik; Terezie Pelikanova; Lia Nattero Chavez; Elena Lundberg; Itxaso Rica; Maria A. Martínez...; Marisol Ruiz de A...; Jeanette Wahlberg; Anastasia Katsarou; Ragnar Hanas; Cristina Hernandez; Maria Clemente León; Ana Gómez-Gila; Marcus Lind; Marta Ferrer Lozano; Theo Sas; Ulf Samuelsson; Stepanka Pruhova; Fabricia Dietrich; Sara Puente Marin; Anders Nordlund; Ulf Hannelius; Rosaura Casas
• Keywords: Clinical endpoint

OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion all patients type 1 diabetes (T1D) or a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In multicenter, randomized, placebo-controlled, double-blind trial, 109 aged 12–24 years (mean ± SD 16.4 4.1) duration 7–193 days (88.8 51.4), elevated serum GAD65 autoantibodies, and fasting C-peptide >0.12 nmol/L were recruited. Participants randomized to receive either three injections (1 month apart) 4 μg GAD-alum oral (2,000 IE daily for 120 days) placebo. The primary outcome was change stimulated area under curve [AUC] after mixed-meal tolerance test) between baseline 15 months. RESULTS Primary end point not met full analysis set (treatment effect ratio 1.091 [CI 0.845–1.408]; P = 0.5009). However, GAD-alum–treated carrying HLA DR3-DQ2 (n 29; defined as DRB1*03, DQB1*02:01) showed greater preservation AUC 1.557 1.126–2.153]; 0.0078) months compared individuals receiving placebo same genotype 17). Several secondary points supporting trends, positive seen partial remission (insulin dose–adjusted HbA1c ≤9; 0.0310). Minor transient injection site reactions reported. CONCLUSION Intralymphatic administration is simple, well-tolerated treatment that together seems preserve recent-onset T1D DR3-DQ2. This constitutes disease-modifying precision medicine approach.