Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

NCT ID: NCT02735031

Last Updated: 2018-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-21
• Study Completion Date: 2018-04-09

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.

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EXENATIDE

Exenatide

• week 1-2: 5 µg twice daily
• week 3-6: 10 µg twice daily (if tolerated)

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

6 weeks treatment with exenatide on top of insulin treatment

PLACEBO

Placebo matched to exenatide

• week 1-2: 5 µg twice daily
• week 3-6: 10 µg twice daily (if tolerated)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

6 weeks treatment with placebo on top of insulin treatment

Interventions

Exenatide

6 weeks treatment with exenatide on top of insulin treatment

Intervention Type: DRUG

Placebo

6 weeks treatment with placebo on top of insulin treatment

Intervention Type: DRUG

Other Intervention Names

Byetta

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radboud university medical centre

Nijmegen, , Netherlands

Countries

Netherlands

Other Identifiers

ESR-15-10862

Identifier Type: -

Identifier Source: org_study_id