Diabetes Mellitus, Type 1Phase 2/3NCT02735031
Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes
A Phase 2/3 study testing Exenatide in people with Diabetes Mellitus, Type 1 and Hypoglycemia, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type 1, Hypoglycemia
- What is being tested?
- Exenatide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Feb 2017to 9 Apr 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Diabetes Mellitus, Type 1, Hypoglycemia
- Being tested
- Exenatide, Placebo
- Keywords
- Glucagon-Like Peptide 1, Impaired hypoglycemic awareness
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExenatideDrug
Also called Byetta
6 weeks treatment with exenatide on top of insulin treatment
PlaceboDrug
6 weeks treatment with placebo on top of insulin treatment
| Study group | Role | What they receive |
|---|---|---|
| EXENATIDE | Active comparator | Exenatide
* week 1-2: 5 µg twice daily
* week 3-6: 10 µg twice daily (if tolerated) Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptom score in response to insulin-induced hypoglycaemia
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 30 minutes
Secondary outcomes (14)
Adrenaline response to insulin-induced hypoglycaemia
Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 30 minutes
Glucagon response to insulin-induced hypoglycaemia
Measured in plasma during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 30 minutes
Time until glycaemic recovery from hypoglycaemia
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 1 hour
Maximal glucose excursion post-hypoglycaemia
Measured during hyperinsulinemic hypoglycaemic glucose clamps
Measured: 1 hour
Time until glucose peak post-hypoglycaemia
Measured after hyperinsulinemic hypoglycaemic glucose clamps
Measured: 1 hour
Area under the glucose concentration curve post-hypoglycaemia
Measured after hyperinsulinemic hypoglycaemic glucose clamps
Measured: 1 hour
Hunger score post-hypoglycaemia
Measured after hyperinsulinemic hypoglycaemic glucose clamps
Measured: 1 hour
Carbohydrate requirement after recovery from hypoglycaemia
Measured after hyperinsulinemic hypoglycaemic glucose clamps by showing pictures of various carbohydrate-containing snacks and beverages
Measured: 1 hour
Number of severe hypoglycaemic events during follow-up
Measured: 16 weeks
Number of nocturnal hypoglycaemic events during follow-up
Measured: 16 weeks
Number of any hypoglycaemic events during follow-up
Measured: 16 weeks
Number of hypoglycaemic events measured by glucose sensor monitoring
optional (in participants agreeing to wear a continuous glucose sensor for 5 days)
Measured: 1 week
Time spent under hypoglycaemic conditions measured by glucose sensor monitoring
optional (in participants agreeing to wear a continuous glucose sensor for 5 days)
Measured: 1 week
Glucose variability as measured by glucose sensor monitoring
optional (in participants agreeing to wear a continuous glucose sensor for 5 days)
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study start21 Feb 2017
- Primary completion28 Mar 2018
- Study completion9 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02735031
- Sponsor's protocol ID
- ESR-15-10862
- Status last verified
- Apr 2017
- First submitted
- 22 Feb 2016
- Last updated
- 12 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Hypoglycaemic Awareness in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02735031
- Acronym / sponsor ID
- ESR-15-10862
- Conditions
- Diabetes Mellitus, Type 1, Hypoglycemia
- Keywords
- Glucagon-Like Peptide 1, Impaired hypoglycemic awareness
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 21 Feb 2017 (actual)
- Primary completion
- 28 Mar 2018 (actual)
- Study completion
- 9 Apr 2018 (actual)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EXENATIDE | Active comparator | Drug: ExenatideExenatide * week 1-2: 5 µg twice daily * week 3-6: 10 µg twice daily (if tolerated) |
| PLACEBO | Placebo comparator | Drug: PlaceboPlacebo matched to exenatide * week 1-2: 5 µg twice daily * week 3-6: 10 µg twice daily (if tolerated) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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%)
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExenatideAlso: Byetta6 weeks treatment with exenatide on top of insulin treatment | Drug | EXENATIDE |
| Placebo6 weeks treatment with placebo on top of insulin treatment | Drug | PLACEBO |
Primary outcome
Symptom score in response to insulin-induced hypoglycaemia
Time frame: 30 minutes
Measured during hyperinsulinemic hypoglycaemic glucose clamps
14 secondary outcomes
Adrenaline response to insulin-induced hypoglycaemia
Time frame: 30 minutes
Glucagon response to insulin-induced hypoglycaemia
Time frame: 30 minutes
Time until glycaemic recovery from hypoglycaemia
Time frame: 1 hour
Maximal glucose excursion post-hypoglycaemia
Time frame: 1 hour
Time until glucose peak post-hypoglycaemia
Time frame: 1 hour
Area under the glucose concentration curve post-hypoglycaemia
Time frame: 1 hour
Hunger score post-hypoglycaemia
Time frame: 1 hour
Carbohydrate requirement after recovery from hypoglycaemia
Time frame: 1 hour
Number of severe hypoglycaemic events during follow-up
Time frame: 16 weeks
Number of nocturnal hypoglycaemic events during follow-up
Time frame: 16 weeks
Number of any hypoglycaemic events during follow-up
Time frame: 16 weeks
Number of hypoglycaemic events measured by glucose sensor monitoring
Time frame: 1 week
Time spent under hypoglycaemic conditions measured by glucose sensor monitoring
Time frame: 1 week
Glucose variability as measured by glucose sensor monitoring
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2018.
Related trials for Diabetes Mellitus, Type 1
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Exenatide in people with Diabetes Mellitus, Type 1 and Hypoglycemia, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symptom score in response to insulin-induced hypoglycaemia (time frame: 30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2018.