NCT02735031

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2017

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 22, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 12, 2016

Completed
11 months until next milestone

Study Start

First participant enrolled

February 21, 2017

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 28, 2018

Completed
12 days until next milestone

Study Completion

Last participant's last visit for all outcomes

April 9, 2018

Completed
Last Updated

April 12, 2018

Status Verified

April 1, 2017

Enrollment Period

1.1 years

First QC Date

February 22, 2016

Last Update Submit

April 11, 2018

Conditions

Diabetes Mellitus, Type 1Hypoglycemia

Keywords

Glucagon-Like Peptide 1Impaired hypoglycemic awareness

Outcome Measures

Primary Outcomes (1)

  • Symptom score in response to insulin-induced hypoglycaemia

    Measured during hyperinsulinemic hypoglycaemic glucose clamps

    30 minutes

Secondary Outcomes (14)

  • Adrenaline response to insulin-induced hypoglycaemia

    30 minutes

  • Glucagon response to insulin-induced hypoglycaemia

    30 minutes

  • Time until glycaemic recovery from hypoglycaemia

    1 hour

  • Maximal glucose excursion post-hypoglycaemia

    1 hour

  • Time until glucose peak post-hypoglycaemia

    1 hour

  • +9 more secondary outcomes

Other Outcomes (2)

  • Pulse rate

    6 weeks

  • Gastrointestinal side effects

    16 weeks

Study Arms (2)

EXENATIDE

ACTIVE COMPARATOR

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

Drug: Exenatide

PLACEBO

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

ExenatideDRUG

6 weeks treatment with exenatide on top of insulin treatment

Also known as: Byetta
EXENATIDE
PlaceboDRUG

6 weeks treatment with placebo on top of insulin treatment

PLACEBO

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud university medical centre

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Hypoglycemia

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

PeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological Factors

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 22, 2016

First Posted

April 12, 2016

Study Start

February 21, 2017

Primary Completion

March 28, 2018

Study Completion

April 9, 2018

Last Updated

April 12, 2018

Record last verified: 2017-04

Locations

NL(1)