BACKGROUND: Type 1 diabetes results from a T-cell mediated autoimmune destruction of insulin-producing pancreatic beta-cells. The 60-kDa heat-shock protein (hsp60) is one of the known target self-antigens. An immunogenic peptide from hsp60, p277, arrested beta-cell destruction and maintained insulin production in newly diabetic non-obese diabetic (NOD) mice. A randomized, double-blind, phase Ib/II study of peptide treatment was undertaken in recent onset type 1 diabetes patients with remaining insulin production. METHODS:Forty-eight recent onset type 1 diabetes patients were assigned subcutaneous injections of 0.2, 1.0 or 2.5 mg peptide DiaPep277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or four placebo injections (n = 12). The primary clinical endpoints were safety and efficacy (glucagon-stimulated C-peptide production at 6 and 12 months); secondary endpoints were HbA1c levels and daily insulin dose adjusted for body weight at 2, 6, 12 and 18 months. RESULTS:C-peptide levels decreased over time in all groups except the 2.5 mg-treated. The decrease in C-peptide production was less in treated patients versus placebo, mostly in the 2.5 mg group. HbA1c increased significantly in the 1.0 mg group and in the 2.5 mg group at 2 and 18 months, respectively. No differences were seen in daily insulin doses. One patient was withdrawn from the study possibly owing to a treatment-related adverse event. CONCLUSIONS: Multiple DiaPep277 peptide administration seems safe and may have a beneficial effect on C-peptide levels over time, but this finding is not supported by lower HbA1c levels or daily insulin requirement. Further investigation on a larger scale is warranted. Copyright 2006 John Wiley & Sons, Ltd.
RCT Entities:
BACKGROUND: Type 1 diabetes results from a T-cell mediated autoimmune destruction of insulin-producing pancreatic beta-cells. The 60-kDa heat-shock protein (hsp60) is one of the known target self-antigens. An immunogenic peptide from hsp60, p277, arrested beta-cell destruction and maintained insulin production in newly diabetic non-obese diabetic (NOD) mice. A randomized, double-blind, phase Ib/II study of peptide treatment was undertaken in recent onset type 1 diabetespatients with remaining insulin production. METHODS: Forty-eight recent onset type 1 diabetespatients were assigned subcutaneous injections of 0.2, 1.0 or 2.5 mg peptide DiaPep277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or four placebo injections (n = 12). The primary clinical endpoints were safety and efficacy (glucagon-stimulated C-peptide production at 6 and 12 months); secondary endpoints were HbA1c levels and daily insulin dose adjusted for body weight at 2, 6, 12 and 18 months. RESULTS: C-peptide levels decreased over time in all groups except the 2.5 mg-treated. The decrease in C-peptide production was less in treated patients versus placebo, mostly in the 2.5 mg group. HbA1c increased significantly in the 1.0 mg group and in the 2.5 mg group at 2 and 18 months, respectively. No differences were seen in daily insulin doses. One patient was withdrawn from the study possibly owing to a treatment-related adverse event. CONCLUSIONS: Multiple DiaPep277 peptide administration seems safe and may have a beneficial effect on C-peptide levels over time, but this finding is not supported by lower HbA1c levels or daily insulin requirement. Further investigation on a larger scale is warranted. Copyright 2006 John Wiley & Sons, Ltd.