Abstract
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 HbA~1c~ 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. HbA~1c~ 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 One patient was withdrawn from the study possibly owing to a treatment‐related adverse event.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 HbA~1c~ levels or daily insulin requirement. Further investigation on a larger scale is warranted. Copyright © 2006 John Wiley & Sons, Ltd.