Sulfonylurea Effects on Glucagon Regulation During Hypoglycemia in Type 1 DM

Condition(s) targeted: Diabetes Mellitus, Type 1

Intervention: glibenclamide (Drug); placebo (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: University Hospital, Basel, Switzerland

Official(s) and/or principal investigator(s):
Stefan Bilz, MD, Principal Investigator, Affiliation: University Hospital, Basel, Switzerland

We aim to demonstrate that oral administration of glibenclamide stimulates pancreatic glucagon secretion during hypoglycemia in insulin-deficient (C-peptide negative) patients with type 1 diabetes when compared to type 1 diabetic patients with residual insulin secretion (C-peptide positive).

Official title: Effect of a Sulfonylurea Compound on the Glucagon Response to Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Primary outcome: plasma glucagon concentrations during insulin induced hypoglycemia with and without glibenclamide pretreatment

Secondary outcome:

rate of glucose recovery following insulin induced hypoglycemia with and without glibenclamide pretreatment

cognitive function during insulin induced hypoglycemia with and without glibenclamide pretreatment

Detailed description: The glucagon response during insulin induced hypoglycemia and rate of glucose recovery will be monitored in 10 C-peptide positive and 10 C-Peptide negative patients with type 1 DM following the application of glibenclamide and placebo in a randomized, single-blind, cross-over study. Cognitive function during hypoglycemia with and without glibenclamide pretreatment will be a secondary outcome.

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients aged 18 to 50 years

- Patients diagnosed with C-peptide negative diabetes type 1 (C-peptide <200 pmol/L 6

min after 1 mg glucagon i. v. at plasma glucose concentrations between 5 and 11 mmol/l)

- Patients diagnosed with C-peptide positive diabetes type 1 (C-peptide > 500 pmol/l 6

min after 1 mg glucagon i. v. at plasma glucose concentrations between 5 and 11 mmol/l)

- Stable metabolic control; HbA1c levels <8. 0 % and without episodes of antecedent

severe hypoglycemias in the past four weeks Exclusion Criteria:

- Patients treated with medications potentially interfering with glucose metabolism,

such as systemic steroids, immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus), highly active antiretroviral therapy

- History coronary artery disease

- History of epilepsy or seizures

- Current smokers

- Any significant or unstable hepatic, cardiac, pulmonary, renal, neurological,

musculoskeletal, hematological or endocrine disease.

- Pregnant or breast feeding women

- Woman of childbearing potential not using a reliable method of birth control such as

oral contraceptives or IUD.

- Subjects refusing or unable to give written informed consent

University Hospital Basel, Basel 4031, Switzerland

Starting date: June 2007
Last updated: March 8, 2012