%0 Journal Article
%A Ludvigsson, Johnny
%A Sumnik, Zdenek
%A Pelikanova, Terezie
%A Nattero-Chavez, Lia
%A Lundberg, Elena
%A Rica, Itxaso
%A Martinez-Brocca, Maria A
%A Ruiz-de-Adana, Marisol
%A Wahlberg, Jeanette
%A Katsarou, Anastasia
%A Hanas, Ragnar
%A Hernandez, Cristina
%A Clemente-Leon, Maria
%A Gomez-Gila, Ana
%A Lind, Marcus
%A Ferrer-Lozano, Marta 
%A Sas, Theo
%A Samuelsson, Ulf
%A Pruhova, Stepanka
%A Dietrich, Fabricia
%A Puente-Marin, Sara
%A Nordlund, Anders
%A Hannelius, Ulf
%A Casas, Rosaura
%T Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial.
%D 2021
%U http://hdl.handle.net/10668/17817
%X To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7-193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported. Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
%K Diabetes Mellitus, Type 1
%K Insulin
%K C-Peptide
%K Glycated Hemoglobin
%K HLA-DR3 Antigen
%K Insulin Secretion
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