Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

• Sponsor: Radboud University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02735031
• Collaborator: AstraZeneca (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.5
• Patients Per Site Per Month: 0.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1; Hypoglycemia	Drug: Exenatide; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• 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: Feb 21, 2017
• Actual Primary Completion Date: Mar 28, 2018
• Actual Study Completion Date: Apr 9, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Symptom score in response to insulin-induced hypoglycaemia [30 minutes]

   Measured during hyperinsulinemic hypoglycaemic glucose clamps

Secondary Outcome Measures

1. Adrenaline response to insulin-induced hypoglycaemia [30 minutes]

   Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps

2. Glucagon response to insulin-induced hypoglycaemia [30 minutes]

   Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps

3. Time until glycaemic recovery from hypoglycaemia [1 hour]

   Measured during hyperinsulinemic hypoglycaemic glucose clamps

4. Maximal glucose excursion post-hypoglycaemia [1 hour]

   Measured during hyperinsulinemic hypoglycaemic glucose clamps

5. Time until glucose peak post-hypoglycaemia [1 hour]

   Measured after hyperinsulinemic hypoglycaemic glucose clamps

6. Area under the glucose concentration curve post-hypoglycaemia [1 hour]

   Measured after hyperinsulinemic hypoglycaemic glucose clamps

7. Hunger score post-hypoglycaemia [1 hour]

   Measured after hyperinsulinemic hypoglycaemic glucose clamps

8. Carbohydrate requirement after recovery from hypoglycaemia [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 [16 weeks]

10. Number of nocturnal hypoglycaemic events during follow-up [16 weeks]

11. Number of any hypoglycaemic events during follow-up [16 weeks]

12. Number of hypoglycaemic events measured by glucose sensor monitoring [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 [1 week]

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

14. Glucose variability as measured by glucose sensor monitoring [1 week]

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

Other Outcome Measures

1. Pulse rate [6 weeks]

   Measured during hyperinsulinemic hypoglycaemic glucose clamps

2. Gastrointestinal side effects [16 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud university medical centre	Nijmegen		Netherlands

Sponsors and Collaborators

• Radboud University Medical Center
• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT02735031
• Other Study ID Numbers: ESR-15-10862
• First Posted: Apr 12, 2016
• Last Update Posted: Apr 12, 2018
• Last Verified: Apr 1, 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Radboud University Medical Center: Glucagon-Like Peptide 1; Impaired hypoglycemic awareness
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Exenatide

Study Results

No Results Posted as of Apr 12, 2018