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Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

Primary Purpose

Diabetes Mellitus, Type 1, Hypoglycemia

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Exenatide
Placebo
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Glucagon-Like Peptide 1, Impaired hypoglycemic awareness

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Radboud university medical centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

EXENATIDE

PLACEBO

Arm Description

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

Placebo matched to exenatide week 1-2: 5 µg twice daily week 3-6: 10 µg twice daily (if tolerated)

Outcomes

Primary Outcome Measures

Symptom score in response to insulin-induced hypoglycaemia
Measured during hyperinsulinemic hypoglycaemic glucose clamps

Secondary Outcome Measures

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

Full Information

First Posted
February 22, 2016
Last Updated
April 11, 2018
Sponsor
Radboud University Medical Center
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02735031
Brief Title
Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes
Official Title
Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Hypoglycaemic Awareness in Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 21, 2017 (Actual)
Primary Completion Date
March 28, 2018 (Actual)
Study Completion Date
April 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1, Hypoglycemia
Keywords
Glucagon-Like Peptide 1, Impaired hypoglycemic awareness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EXENATIDE
Arm Type
Active Comparator
Arm Description
Exenatide week 1-2: 5 µg twice daily week 3-6: 10 µg twice daily (if tolerated)
Arm Title
PLACEBO
Arm Type
Placebo Comparator
Arm Description
Placebo matched to exenatide week 1-2: 5 µg twice daily week 3-6: 10 µg twice daily (if tolerated)
Intervention Type
Drug
Intervention Name(s)
Exenatide
Other Intervention Name(s)
Byetta
Intervention Description
6 weeks treatment with exenatide on top of insulin treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
6 weeks treatment with placebo on top of insulin treatment
Primary Outcome Measure Information:
Title
Symptom score in response to insulin-induced hypoglycaemia
Description
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
30 minutes
Secondary Outcome Measure Information:
Title
Adrenaline response to insulin-induced hypoglycaemia
Description
Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
30 minutes
Title
Glucagon response to insulin-induced hypoglycaemia
Description
Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
30 minutes
Title
Time until glycaemic recovery from hypoglycaemia
Description
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
1 hour
Title
Maximal glucose excursion post-hypoglycaemia
Description
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
1 hour
Title
Time until glucose peak post-hypoglycaemia
Description
Measured after hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
1 hour
Title
Area under the glucose concentration curve post-hypoglycaemia
Description
Measured after hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
1 hour
Title
Hunger score post-hypoglycaemia
Description
Measured after hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
1 hour
Title
Carbohydrate requirement after recovery from hypoglycaemia
Description
Measured after hyperinsulinemic hypoglycaemic glucose clamps by showing pictures of various carbohydrate-containing snacks and beverages
Time Frame
1 hour
Title
Number of severe hypoglycaemic events during follow-up
Time Frame
16 weeks
Title
Number of nocturnal hypoglycaemic events during follow-up
Time Frame
16 weeks
Title
Number of any hypoglycaemic events during follow-up
Time Frame
16 weeks
Title
Number of hypoglycaemic events measured by glucose sensor monitoring
Description
optional (in participants agreeing to wear a continuous glucose sensor for 5 days)
Time Frame
1 week
Title
Time spent under hypoglycaemic conditions measured by glucose sensor monitoring
Description
optional (in participants agreeing to wear a continuous glucose sensor for 5 days)
Time Frame
1 week
Title
Glucose variability as measured by glucose sensor monitoring
Description
optional (in participants agreeing to wear a continuous glucose sensor for 5 days)
Time Frame
1 week
Other Pre-specified Outcome Measures:
Title
Pulse rate
Description
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Time Frame
6 weeks
Title
Gastrointestinal side effects
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Radboud university medical centre
City
Nijmegen
Country
Netherlands

12. IPD Sharing Statement

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