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

  • Netherlands
      • 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

  • 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 Names:
  • 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

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.

Sponsor

Radboud University Medical Center

Collaborators

AstraZeneca

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

Keywords

Additional Relevant MeSH Terms

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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