- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02735031
Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes
April 11, 2018 updated by: Radboud University Medical Center
Effect of the GLP-1 Receptor Agonist Exenatide on 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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Nijmegen, Netherlands
- Radboud University Medical Centre
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: EXENATIDE
Exenatide
|
6 weeks treatment with exenatide on top of insulin treatment
Other Names:
|
Placebo Comparator: PLACEBO
Placebo matched to exenatide
|
6 weeks treatment with placebo on top of insulin treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Symptom score in response to insulin-induced hypoglycaemia
Time Frame: 30 minutes
|
Measured during hyperinsulinemic hypoglycaemic glucose clamps
|
30 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adrenaline response to insulin-induced hypoglycaemia
Time Frame: 30 minutes
|
Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps
|
30 minutes
|
Glucagon response to insulin-induced hypoglycaemia
Time Frame: 30 minutes
|
Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps
|
30 minutes
|
Time until glycaemic recovery from hypoglycaemia
Time Frame: 1 hour
|
Measured during hyperinsulinemic hypoglycaemic glucose clamps
|
1 hour
|
Maximal glucose excursion post-hypoglycaemia
Time Frame: 1 hour
|
Measured during hyperinsulinemic hypoglycaemic glucose clamps
|
1 hour
|
Time until glucose peak post-hypoglycaemia
Time Frame: 1 hour
|
Measured after hyperinsulinemic hypoglycaemic glucose clamps
|
1 hour
|
Area under the glucose concentration curve post-hypoglycaemia
Time Frame: 1 hour
|
Measured after hyperinsulinemic hypoglycaemic glucose clamps
|
1 hour
|
Hunger score post-hypoglycaemia
Time Frame: 1 hour
|
Measured after hyperinsulinemic hypoglycaemic glucose clamps
|
1 hour
|
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
|
1 hour
|
Number of severe hypoglycaemic events during follow-up
Time Frame: 16 weeks
|
16 weeks
|
|
Number of nocturnal hypoglycaemic events during follow-up
Time Frame: 16 weeks
|
16 weeks
|
|
Number of any hypoglycaemic events during follow-up
Time Frame: 16 weeks
|
16 weeks
|
|
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)
|
1 week
|
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)
|
1 week
|
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)
|
1 week
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pulse rate
Time Frame: 6 weeks
|
Measured during hyperinsulinemic hypoglycaemic glucose clamps
|
6 weeks
|
Gastrointestinal side effects
Time Frame: 16 weeks
|
16 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 21, 2017
Primary Completion (Actual)
March 28, 2018
Study Completion (Actual)
April 9, 2018
Study Registration Dates
First Submitted
February 22, 2016
First Submitted That Met QC Criteria
April 6, 2016
First Posted (Estimate)
April 12, 2016
Study Record Updates
Last Update Posted (Actual)
April 12, 2018
Last Update Submitted That Met QC Criteria
April 11, 2018
Last Verified
April 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Hypoglycemia
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Obesity Agents
- Incretins
- Exenatide
Other Study ID Numbers
- ESR-15-10862
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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