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Completed

NCT Number: NCT02735031

Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

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.

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Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hypoglycemia Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Radboud university medical centre

Nijmegen, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

exenatide

Drug

6 weeks treatment with exenatide on top of insulin treatment

Other names: Byetta

Placebo

Drug

6 weeks treatment with placebo on top of insulin treatment

Primary outcomes

  1. Symptom score in response to insulin-induced hypoglycaemia

    Time frame: 30 minutes

    Measured during hyperinsulinemic hypoglycaemic glucose clamps

Secondary outcomes

  1. Adrenaline response to insulin-induced hypoglycaemia

    Time frame: 30 minutes

    Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps

  2. Glucagon response to insulin-induced hypoglycaemia

    Time frame: 30 minutes

    Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps

  3. Time until glycaemic recovery from hypoglycaemia

    Time frame: 1 hour

    Measured during hyperinsulinemic hypoglycaemic glucose clamps

  4. Maximal glucose excursion post-hypoglycaemia

    Time frame: 1 hour

    Measured during hyperinsulinemic hypoglycaemic glucose clamps

  5. Time until glucose peak post-hypoglycaemia

    Time frame: 1 hour

    Measured after hyperinsulinemic hypoglycaemic glucose clamps

  6. Area under the glucose concentration curve post-hypoglycaemia

    Time frame: 1 hour

    Measured after hyperinsulinemic hypoglycaemic glucose clamps

  7. Hunger score post-hypoglycaemia

    Time frame: 1 hour

    Measured after hyperinsulinemic hypoglycaemic glucose clamps

  8. Carbohydrate requirement after recovery from hypoglycaemia

    Time frame: 1 hour

    Measured after hyperinsulinemic hypoglycaemic glucose clamps by showing pictures of various carbohydrate-containing snacks and beverages

  9. Number of severe hypoglycaemic events during follow-up

    Time frame: 16 weeks

  10. Number of nocturnal hypoglycaemic events during follow-up

    Time frame: 16 weeks

  11. Number of any hypoglycaemic events during follow-up

    Time frame: 16 weeks

  12. Number of hypoglycaemic events measured by glucose sensor monitoring

    Time frame: 1 week

    optional (in participants agreeing to wear a continuous glucose sensor for 5 days)

  13. Time spent under hypoglycaemic conditions measured by glucose sensor monitoring

    Time frame: 1 week

    optional (in participants agreeing to wear a continuous glucose sensor for 5 days)

  14. Glucose variability as measured by glucose sensor monitoring

    Time frame: 1 week

    optional (in participants agreeing to wear a continuous glucose sensor for 5 days)

Other outcomes

  1. Pulse rate

    Time frame: 6 weeks

    Measured during hyperinsulinemic hypoglycaemic glucose clamps

  2. Gastrointestinal side effects

    Time frame: 16 weeks

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • AstraZeneca

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Apr 12, 2016
Registry last updated
Apr 12, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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