Aktuelle studien zur immun-intervention bei neumanifestem typ-1-diabetes

In recent years, the Diabetes Prevention Trial (DPT) 1, the largest diabetes prevention study until today, has been the clinical research focus on β-cell immunotherapy. Insulin prophylaxis was not protective in individuals at high risk for type 1 diabetes. Nonetheless, DPT-1 showed that antigen therapy still had immunoregulatory effects in late stages of the autoimmune process. TrialNet, which carried out the DPT-1, is a consortium of US groups that has developed a structure for joint performance of future intervention trials. In Europe, the ENDIT forum, which carries out the European Nicotinamid intervention trial, is currently making efforts to set up a similar network for Europe called InterVene. This review describes intervention trials in newly diagnosed type 1 diabetes (T1DM) that are being currently performed in Europe with participating centers in Germany. Primary endpoint in all these studies is preservation of β-cell reserve, indicated by measurements of basal and stimulated C-peptide. Secondary end-points include HbA_1c levels, need for insulin, fasting blood glucose levels, and monitoring of cellular and humoral immune responses. 1) Centers in Belgium, Paris, and Munich currently recruiting 80 adult patients with recent onset T1DM into a placebo-controlled, doubleblind Phase II trial that evaluates the effect of treatment with the non-mitogenic, monoclonal CD3-antibody YTH 12.5 (ChAgly CD3), applied intravenously on six consecutive days with a follow up of 18 months. 2) Centers in Leipzig and Munich are participating in a multinational, placebo-controlled Phase 2 trial that tests subcutaneous treatment with different doses of the altered peptide ligand APL-NBI-6024 applied monthly over 24 months in 388 adolescent and adult patients with recent onset T1DM. 3) In Munich, an open, controlled trial has started that evaluate daily oral treatment with 0.25 μg 1,25-Dihydroxy-Vitamine D3 over 9 months in 20 patients with newly diagnosed T1DM. 4) A European multicenter Phase 2 secondary intervention trial with centers in Düsseldorf (DDFI), London, and Rome is investigating the effects of the immunomodulatory peptide p277 (DiaPep277) in GAD positive adult diabetic patients on the endpoints stimulated C-peptide, as well as the need and time for insulin. In a study from Israel, the heat-shock protein derived DiaPep277 was successfully tested in newly diagnosed T1DM and showed preservation of endogenous β-cell reserve during a course of 10 months compared with untreated control individuals who showed progressive loss of stimulated C-peptide.