Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 1; Hypoglycemia
• Interventions: Drug: Exenatide; Drug: Placebo

• Registration Number: NCT02735031
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-02-22
• Study First Submitted QC: 2016-04-06
• Study First Posted: 2016-04-12
• Study Start: 2017-02-21
• Status Verified: 2017-04
• Primary Completion: 2018-03-28
• Study Completion: 2018-04-09
• Last Update Submitted: 2018-04-11
• Last Update Posted: 2018-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
EXENATIDE	Exenatide	Exenatide * week 1-2: 5 µg twice daily * week 3-6: 10 µg twice daily (if tolerated)
PLACEBO	Placebo	Placebo matched to exenatide * week 1-2: 5 µg twice daily * week 3-6: 10 µg twice daily (if tolerated)

Primary Outcome Measures

Name	Time	Method
Symptom score in response to insulin-induced hypoglycaemia	30 minutes	Measured during hyperinsulinemic hypoglycaemic glucose clamps

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Radboud university medical centre; 🇳🇱 Nijmegen, Netherlands