Clinical trial NCT01272583: Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery
Official title: Effects of 6 Weeks Treatment With a Dipeptidyl Peptidase 4 Inhibitor on Counterregulatory and Incretin Hormones During Acute Hypoglycaemia in Patients With Type 1 Diabetes: a Randomized Double Blind Placebo-controlled Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Hypoglycemia
Keywords: Type 1 diabetes
DPP-4 inhibitor
Glucagon
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-01-10
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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. Dipeptidyl Peptidase (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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Type 1 Diabetes Mellitus 5-20 years duration
* C-peptide negative
* Willing and able to give written informed consent

Exclusion Criteria:

* Impaired awareness of hypoglycaemia
* BMI \> 27 kg/m2
* Evidence of severe diabetes complications (autonomic neuropathy, macroalbuminuria, proliferative retinopathy)
* Acute illness within 3 months before the study
* Significant renal impairment (creatinine clearance \< 50ml/min)
* Use of beta-adrenoreceptor blockers
* Cardiac history (previous arrhythmia)
* History of epilepsy

Primary outcomes:
measure: Glucagon Response to Acute Hypoglycaemia
timeFrame: Change from initialisation phase to 40 minutes after onset of hypoglycaemia
measure: Glucagon Response to Acute Hypoglycaemia
timeFrame: 0, 10, 20 and 40 minutes
Secondary outcomes:
measure: Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
timeFrame: 0, 10, 20, 40 minutes
measure: Epinephrine Response to Acute Hypoglycaemia
timeFrame: 0, 10, 20, 40 minutes
measure: Norepinephrine Response to Acute Hypoglycaemia
timeFrame: 0, 10, 20, 40 minutes
measure: Growth Hormone Response to Acute Hypoglycaemia
timeFrame: 0, 10, 20, 40 minutes
measure: Cortisol Response to Acute Hypoglycaemia
timeFrame: 0, 10, 20, 40 minutes
measure: Symptomatic Hormone Responses to Acute Hypoglycaemia.
timeFrame: Change from baseline symptomatic response at hypoglycaemia and 30 minutes after hypoglycaemia
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: Noord Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Frits Holleman, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: