Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Hypoglycaemic Awareness in Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02735031
• Other study ID #: ESR-15-10862
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 22, 2016
• Last updated: April 11, 2018
• Start date: February 21, 2017
• Est. completion date: April 9, 2018

Study information

• Verified date: April 2017
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: April 9, 2018
• Est. primary completion date: March 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• Exenatide
6 weeks treatment with exenatide on top of insulin treatment
• Placebo
6 weeks treatment with placebo on top of insulin treatment

Locations

Country	Name	City	State
Netherlands	Radboud university medical centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	AstraZeneca

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pulse rate	Measured during hyperinsulinemic hypoglycaemic glucose clamps	6 weeks
Other	Gastrointestinal side effects		16 weeks
Primary	Symptom score in response to insulin-induced hypoglycaemia	Measured during hyperinsulinemic hypoglycaemic glucose clamps	30 minutes
Secondary	Adrenaline response to insulin-induced hypoglycaemia	Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps	30 minutes
Secondary	Glucagon response to insulin-induced hypoglycaemia	Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps	30 minutes
Secondary	Time until glycaemic recovery from hypoglycaemia	Measured during hyperinsulinemic hypoglycaemic glucose clamps	1 hour
Secondary	Maximal glucose excursion post-hypoglycaemia	Measured during hyperinsulinemic hypoglycaemic glucose clamps	1 hour
Secondary	Time until glucose peak post-hypoglycaemia	Measured after hyperinsulinemic hypoglycaemic glucose clamps	1 hour
Secondary	Area under the glucose concentration curve post-hypoglycaemia	Measured after hyperinsulinemic hypoglycaemic glucose clamps	1 hour
Secondary	Hunger score post-hypoglycaemia	Measured after hyperinsulinemic hypoglycaemic glucose clamps	1 hour
Secondary	Carbohydrate requirement after recovery from hypoglycaemia	Measured after hyperinsulinemic hypoglycaemic glucose clamps by showing pictures of various carbohydrate-containing snacks and beverages	1 hour
Secondary	Number of severe hypoglycaemic events during follow-up		16 weeks
Secondary	Number of nocturnal hypoglycaemic events during follow-up		16 weeks
Secondary	Number of any hypoglycaemic events during follow-up		16 weeks
Secondary	Number of hypoglycaemic events measured by glucose sensor monitoring	optional (in participants agreeing to wear a continuous glucose sensor for 5 days)	1 week
Secondary	Time spent under hypoglycaemic conditions measured by glucose sensor monitoring	optional (in participants agreeing to wear a continuous glucose sensor for 5 days)	1 week
Secondary	Glucose variability as measured by glucose sensor monitoring	optional (in participants agreeing to wear a continuous glucose sensor for 5 days)	1 week