Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery (DARE)
Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. DPP-4 inhibitors augment the glucagon response to insulin-induced hypoglycaemia in type 2 diabetes. The investigators hypothesize that treatment with a DPP-4 inhibitor in patients with type 1 diabetes will recover the alpha cell response to hypoglycaemia.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
|Official Title:||Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery|
- Glucagon response to insulin induced hypoglycaemia [ Time Frame: Change from baseline in glucagon concentration at 40 minutes after hypoglycaemia ] [ Designated as safety issue: No ]Glucagon response to insulin induced hypoglycaemia measured as AUC (area under the curve)
- other counterregulatory hormones, GLP-1 and GIP [ Time Frame: Change from baseline in counterregulatory hormones concentration at 40 minutes after hypoglycaemia ] [ Designated as safety issue: No ]the counterregulatory hormone responses to insulin induced hypoglycaemia measured as AUC
- Symptomatic hormone responses to insulin induced hypoglycaemia. [ Time Frame: Change from baseline symptomatic respons at hypoglycaemia and 30 minutes after hypoglycaemia ] [ Designated as safety issue: No ]Symptomatic hormone responses to insulin induced hypoglycaemia are measured with an adapted hypoglycaemia score system.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||September 2012|
|Estimated Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
The 16 type 1 patients will be randomised to one of two treatment sequences: DPP-4 inhibitor followed by placebo or placebo followed by a DPP-4 inhibitor. Each treatment period lasts 6 weeks, so all patients will receive treatment for 12 weeks in total. Induction of hypoglycaemia will take place at 0 weeks, 6 weeks and 12 weeks to determine the glucagon response.
|Academic Medical Center|
|Amsterdam, Noord Holland, Netherlands, 1100DD|
|Principal Investigator:||Frits Holleman, MD,PhD||Academic Medical Center, Amsterdam|