RT Journal Article
T1 Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial.
A1 Ludvigsson, Johnny
A1 Sumnik, Zdenek
A1 Pelikanova, Terezie
A1 Nattero-Chavez, Lia
A1 Lundberg, Elena
A1 Rica, Itxaso
A1 Martinez-Brocca, Maria A
A1 Ruiz-de-Adana, Marisol
A1 Wahlberg, Jeanette
A1 Katsarou, Anastasia
A1 Hanas, Ragnar
A1 Hernandez, Cristina
A1 Clemente-Leon, Maria
A1 Gomez-Gila, Ana
A1 Lind, Marcus
A1 Ferrer-Lozano, Marta
A1 Sas, Theo
A1 Samuelsson, Ulf
A1 Pruhova, Stepanka
A1 Dietrich, Fabricia
A1 Puente-Marin, Sara
A1 Nordlund, Anders
A1 Hannelius, Ulf
A1 Casas, Rosaura
K1 Diabetes Mellitus, Type 1
K1 Insulin
K1 C-Peptide
K1 Glycated Hemoglobin
K1 HLA-DR3 Antigen
K1 Insulin Secretion
AB 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.
PB American Diabetes Association
YR 2021
FD 2021-04-15
LK http://hdl.handle.net/10668/17817
UL http://hdl.handle.net/10668/17817
LA en
NO Ludvigsson J, Sumnik Z, Pelikanova T, Nattero Chavez L, Lundberg E, Rica I, et al.  Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial. Diabetes Care. 2021 Jul;44(7):1604-1612
DS RISalud
RD Jul 1, 2025