Clinical trial NCT02735031: Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes
Official title: Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Hypoglycaemic Awareness in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diabetes Mellitus, Type 1
Hypoglycemia
Keywords: Glucagon-Like Peptide 1
Impaired hypoglycemic awareness
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2016-04-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired hypoglycaemic awareness (IHA) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IHA is usually the end-result of a process of habituation to recurrent hypoglycemia that is potentially reversible. Treatment with glucagon-like peptide (GLP)-1 Receptor Agonists (1RAs) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the GLP-1RA, exenatide, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IHA. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 6 weeks with exenatide (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.


Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes, disease duration \>1 year
* Age \>18 years, \<70 years
* Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
* Impaired hypoglycaemic awareness as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire
* Glycated haemoglobin (HbA1c) ≥42 mmol/mol (6%) and ≤75 mmol/mol (9.0%)
* Ability to provide informed consent

Exclusion Criteria:

* Treatment with incretin-based therapy
* Known intolerance to GLP-1RAs (including allergy)
* Treatment with glucose-modifying or immune-modifying agents, e.g. prednisolon
* Recent history of myocardial infarction or stroke (past year) or laser coagulation for proliferative retinopathy (past 6 months)
* Proliferative retinopathy
* Symptomatic diabetic neuropathy
* Diabetic nephropathy as reflected by albumin-creatinin ratio \>30 mmol/mg or estimated Glomerular Filtration Rate (eGFR) \<60 ml/min/1.73 m2
* Known heart failure
* History of pancreatitis (acute or chronic) or pancreatic cancer
* Body-mass index \>40 kg/m2
* Use of premixed insulin or of long-acting insulin alone
* Total daily insulin dose requirements \<20 units unless on pump treatment
* Pregnancy or unwillingness to undertake measures for birth control

Primary outcomes:
measure: Symptom score in response to insulin-induced hypoglycaemia
timeFrame: 30 minutes
Secondary outcomes:
measure: Adrenaline response to insulin-induced hypoglycaemia
timeFrame: 30 minutes
measure: Glucagon response to insulin-induced hypoglycaemia
timeFrame: 30 minutes
measure: Time until glycaemic recovery from hypoglycaemia
timeFrame: 1 hour
measure: Maximal glucose excursion post-hypoglycaemia
timeFrame: 1 hour
measure: Time until glucose peak post-hypoglycaemia
timeFrame: 1 hour
measure: Area under the glucose concentration curve post-hypoglycaemia
timeFrame: 1 hour
measure: Hunger score post-hypoglycaemia
timeFrame: 1 hour
measure: Carbohydrate requirement after recovery from hypoglycaemia
timeFrame: 1 hour
measure: Number of severe hypoglycaemic events during follow-up
timeFrame: 16 weeks
measure: Number of nocturnal hypoglycaemic events during follow-up
timeFrame: 16 weeks
measure: Number of any hypoglycaemic events during follow-up
timeFrame: 16 weeks
measure: Number of hypoglycaemic events measured by glucose sensor monitoring
timeFrame: 1 week
measure: Time spent under hypoglycaemic conditions measured by glucose sensor monitoring
timeFrame: 1 week
measure: Glucose variability as measured by glucose sensor monitoring
timeFrame: 1 week
Other outcomes:
measure: Pulse rate
timeFrame: 6 weeks
measure: Gastrointestinal side effects
timeFrame: 16 weeks
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud university medical centre
Study officials:
References: