title: GAD-treatment of children and adolescents with recent-onset type 1 diabetes preserves residual insulin secretion after 30 months.
abstract: BACKGROUND
  This study aimed to analyse data from two different studies (phase II and phase III) regarding the safety and efficacy of treatment with alum formulated glutamic acid decarboxylase GAD65 (GAD-alum) at 30 months after administration to children and adolescents with type 1 diabetes.
  
  
  METHODS
  The phase II trial was a double-blind, randomised placebo-controlled study, including 70 children and adolescents who were followed for 30  months. Participants received a subcutaneous injection of either 20 µg of GAD-alum or placebo at baseline and 1 month later. During a subsequent larger European phase III trial including three treatment arms, participants received two or four subcutaneous injections of either 20 µg of GAD-alum and/or placebo at baseline, 1, 3 and 9  months. The phase III trial was prematurely interrupted at 15 months, but of the 148 Swedish patients, a majority completed the 21 months follow-up, and 45 patients completed the trial at 30 months. Both studies included GAD65 auto-antibodies-positive patients with fasting C-peptide ≥ 0.10 nmol/l. We have now combined the results of these two trials.
  
  
  RESULTS
  There were no treatment related adverse events. In patients treated with 2 GAD-alum doses, stimulated C-peptide area under the curve had decreased significantly less (9  m: p  <  0.037; 15 m: p  <  0.032; 21 m: p  <  0.003 and 30  m: p <  0.004), and a larger proportion of these patients were also able to achieve a peak stimulated C-peptide > 0.2  nmol/L (p  <  0.05), as compared with placebo.
  
  
  CONCLUSIONS
  Treatment with two doses of GAD-alum in children and adolescents with recent-onset type 1 diabetes shows no adverse events and preserves residual insulin secretion.
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Chéramy
authors.forename: Stina
authors.initials: S
authors.lastname: Axelsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Pihl
authors.forename: Linda
authors.initials: L
authors.lastname: Akerman
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
mesh_terms: D000293:Adolescent; D000534:Alum Compounds / Q000627:therapeutic use*; D001323:Autoantibodies; D002096:C-Peptide / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005968:Glutamate Decarboxylase / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D055815:Young Adult
chemical_list: D000534:Alum Compounds; D001323:Autoantibodies; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human; C041524:aluminum sulfate; C401141:glutamate decarboxylase 2
keywords: C-peptide; GAD-alum treatment; GAD65; children; type 1 diabetes