AIMS/HYPOTHESIS: The aim of this study was to ascertain whether treatment of GAD65 autoantibody (GADA)-positive diabetic patients with alum-formulatedrecombinant GAD65 (GAD-alum) is safe and does not compromise beta cell function. METHODS: This Phase 2, placebo-controlled, dose-escalation clinical trial, which was randomized through a central office, was performed in 47 GADA-positive type 2 diabetic patients, who received subcutaneous injections of GAD-alum (4 [n = 9], 20 [n = 8], 100 [n = 9] or 500 [n = 8] microg) orplacebo (n = 13) at weeks 1 and 4 of the trial. Participants and caregivers were blinded to group assignments. The primary outcome was safety as assessed by neurological tests, medications and beta cell function evaluated over 5 years, representing the end of the trial. RESULTS: No severe study-related adverse events occurred during the 5 year follow-up. None of the dose groups was associated with an increased risk of starting insulin treatment compared with the placebo group. The use of oral hypoglycaemic agents did not differ between the dose groups. After 5 years, fasting C-peptide levels declined in the placebo group (-0.24; 95% CI -0.41 to -0.07 log(10) nmol/l; p = 0.01) and the 500 microg dose group (-0.37; 95% CI -0.57 to -0.17 log(10) nmol/l; p = 0.003), but not in the 4 microg (-0.10; 95% CI -0.28 to 0.07 log(10) nmol/l; p = 0.20), 20 microg (0.04; 95% CI -0.12 to 0.19 log(10) nmol/l; p = 0.58) and 100 microg (0.00; 95% CI -0.20 to -0.20 log(10) nmol/l; p = 0.98) dose groups. CONCLUSIONS/ INTERPRETATION: The primary outcome of safety was achieved, since no severe study-related adverse events occurred. TRIAL REGISTRATION: Because the study was initiated before 1 July 2005, the protocol was not registered in a registry.
RCT Entities:
AIMS/HYPOTHESIS: The aim of this study was to ascertain whether treatment of GAD65 autoantibody (GADA)-positive diabeticpatients with alum-formulated recombinant GAD65 (GAD-alum) is safe and does not compromise beta cell function. METHODS: This Phase 2, placebo-controlled, dose-escalation clinical trial, which was randomized through a central office, was performed in 47 GADA-positive type 2 diabeticpatients, who received subcutaneous injections of GAD-alum (4 [n = 9], 20 [n = 8], 100 [n = 9] or 500 [n = 8] microg) or placebo (n = 13) at weeks 1 and 4 of the trial. Participants and caregivers were blinded to group assignments. The primary outcome was safety as assessed by neurological tests, medications and beta cell function evaluated over 5 years, representing the end of the trial. RESULTS: No severe study-related adverse events occurred during the 5 year follow-up. None of the dose groups was associated with an increased risk of starting insulin treatment compared with the placebo group. The use of oral hypoglycaemic agents did not differ between the dose groups. After 5 years, fasting C-peptide levels declined in the placebo group (-0.24; 95% CI -0.41 to -0.07 log(10) nmol/l; p = 0.01) and the 500 microg dose group (-0.37; 95% CI -0.57 to -0.17 log(10) nmol/l; p = 0.003), but not in the 4 microg (-0.10; 95% CI -0.28 to 0.07 log(10) nmol/l; p = 0.20), 20 microg (0.04; 95% CI -0.12 to 0.19 log(10) nmol/l; p = 0.58) and 100 microg (0.00; 95% CI -0.20 to -0.20 log(10) nmol/l; p = 0.98) dose groups. CONCLUSIONS/ INTERPRETATION: The primary outcome of safety was achieved, since no severe study-related adverse events occurred. TRIAL REGISTRATION: Because the study was initiated before 1 July 2005, the protocol was not registered in a registry.
Authors: T Tuomi; A Carlsson; H Li; B Isomaa; A Miettinen; A Nilsson; M Nissén; B O Ehrnström; B Forsén; B Snickars; K Lahti; C Forsblom; C Saloranta; M R Taskinen; L C Groop Journal: Diabetes Date: 1999-01 Impact factor: 9.461
Authors: R Turner; I Stratton; V Horton; S Manley; P Zimmet; I R Mackay; M Shattock; G F Bottazzo; R Holman Journal: Lancet Date: 1997-11-01 Impact factor: 79.321
Authors: Jeffrey P Krischer; David D Cuthbertson; Liping Yu; Tihamer Orban; Noel Maclaren; Richard Jackson; William E Winter; Desmond A Schatz; Jerry P Palmer; George S Eisenbarth Journal: J Clin Endocrinol Metab Date: 2003-01 Impact factor: 5.958
Authors: E Ortqvist; B Brooks-Worrell; K Lynch; J Radtke; L M Bekris; I Kockum; C-D Agardh; C M Cilio; A L Lethagen; B Persson; A Lernmark; J Reichow; S Oak; J P Palmer; C S Hampe Journal: J Clin Endocrinol Metab Date: 2010-08-04 Impact factor: 5.958