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Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT02735031
Recruitment Status : Completed
First Posted : April 12, 2016
Last Update Posted : April 12, 2018
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Radboud University

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Hypoglycemia Drug: Exenatide Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Hypoglycaemic Awareness in Type 1 Diabetes
Actual Study Start Date : February 21, 2017
Actual Primary Completion Date : March 28, 2018
Actual Study Completion Date : April 9, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
Active Comparator: EXENATIDE

Exenatide

  • week 1-2: 5 µg twice daily
  • week 3-6: 10 µg twice daily (if tolerated)
Drug: Exenatide
6 weeks treatment with exenatide on top of insulin treatment
Other Name: Byetta

Placebo Comparator: PLACEBO

Placebo matched to exenatide

  • week 1-2: 5 µg twice daily
  • week 3-6: 10 µg twice daily (if tolerated)
Drug: Placebo
6 weeks treatment with placebo on top of insulin treatment




Primary Outcome Measures :
  1. Symptom score in response to insulin-induced hypoglycaemia [ Time Frame: 30 minutes ]
    Measured during hyperinsulinemic hypoglycaemic glucose clamps


Secondary Outcome Measures :
  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 Outcome Measures:
  1. Pulse rate [ Time Frame: 6 weeks ]
    Measured during hyperinsulinemic hypoglycaemic glucose clamps

  2. Gastrointestinal side effects [ Time Frame: 16 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02735031


Locations
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Netherlands
Radboud university medical centre
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
AstraZeneca

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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02735031     History of Changes
Other Study ID Numbers: ESR-15-10862
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: April 12, 2018
Last Verified: April 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Radboud University:
Glucagon-Like Peptide 1
Impaired hypoglycemic awareness

Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Hypoglycemia
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists