Clinical trial NCT00515801: Sulfonylurea Effects on Glucagon Regulation During Hypoglycemia in Type 1 DM
Official title: Effect of a Sulfonylurea Compound on the Glucagon Response to Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: diabetes mellitus type 1
hypoglycemia
sulfonylurea
glucagon
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2007-08-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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).

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.

Eligibility 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

Primary outcomes:
measure: plasma glucagon concentrations during insulin induced hypoglycemia with and without glibenclamide pretreatment
timeFrame: cross-sectional
Secondary outcomes:
measure: rate of glucose recovery following insulin induced hypoglycemia with and without glibenclamide pretreatment
timeFrame: cross-sectional
measure: cognitive function during insulin induced hypoglycemia with and without glibenclamide pretreatment
timeFrame: cross-sectional
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Stefan Bilz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seelig E, Bilz S, Keller U, Meienberg F, Christ-Crain M. Concentrations of the stress hormone copeptin increase upon hypoglycaemia in patients with type 1 diabetes dependent of hypoglycaemia awareness. PLoS One. 2013 Aug 30;8(8):e72876. doi: 10.1371/journal.pone.0072876. eCollection 2013.