Type 1 Diabetes MellitusPhase 4HypoDegNCT02192450
Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia
A Phase 4 study testing Insulin aspart/glargine and Insulin aspart/degludec in people with Type 1 Diabetes Mellitus and Nocturnal Hypoglycemia, run by Nordsjaellands Hospital at 1 site in Denmark.
Trial summary
The purpose of this study is to determine whether insulin degludec compared to insulin glargine can reduce the risk of symptomatic nocturnal hypoglycaemia in subjects with the greatest potential benefit from optimised insulin treatment, which are patients with type 1 diabetes and high risk of nocturnal severe… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes Mellitus, Nocturnal Hypoglycemia, Recurrent Severe Hypoglycaemia
- What is being tested?
- Insulin aspart/glargine and Insulin aspart/degludec
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 149 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2015to 28 Feb 2019
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes > 5 years
- One or more episodes of nocturnal severe hypoglycaemia during the preceding two years
- Treated with multiple dose insulin injection (>2) or insulin pump. Both human insulin and insulin analogues are allowed
- Willingness to a once daily (OD) regimen concerning insulin degludec and insulin glargine
- Willingness to do self-monitoring of blood glucose (SMBG) and keep a diary
- Signed informed consent
Who cannot join
- History of primary and secondary adrenal insufficiency, growth hormone deficiency, or untreated myxoedema
- History of unstable angina or major cardiovascular events (myocardial infarction, coronary re-vascularisation, transient ischaemic attack, or stroke within the last three months)
- Heart failure, New York Heart Association (NYHA) class IV
- History of malignancy unless a disease-free period exceeding five years
- History of alcohol or drug abuse
- Treatment with glucose lowering agent(s) other than insulin
Show all 12Show fewer
- Pregnant or lactating women
- Women of childbearing potential who are not using chemical (P-pills or gestagen depots) or mechanical (intra-uterine device) contraception
- Participation in another investigational drug study within the last 3 months
- Inability to understand the informed consent
- HbA1c > 86 mmol/mol (10%)
- Shifting working hours
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Insulin Degludec on Risk of Symptomatic Nocturnal Hypoglycaemia in Subjects With Type 1 Diabetes and High Risk of Nocturnal Severe Hypoglycaemia
The purpose of this study is to determine whether insulin degludec compared to insulin glargine can reduce the risk of symptomatic nocturnal hypoglycaemia in subjects with the greatest potential benefit from optimised insulin treatment, which are patients with type 1 diabetes and high risk of nocturnal severe hypoglycaemia.
Read the detailed description
Background: Insulin degludec is a novel insulin analogue that may reduce the risk of mild nocturnal hypoglycaemia in type 1 diabetes. Patients with type 1 diabetes and recurrent severe hypoglycaemia (high risk patients) are also burdened by nocturnal hyoglycaemia (mild and silent). These episodes may contribute to the developement of hormonal counterregulatory failure and hypoglycaemia unawareness, which in turn increases the risk of further hypoglycaemic episodes, especially epiosdes of severe hypoglycaemia.The effect of insulin degludec on risk of mild nocturnal hypoglycaemia in subjects with type 1 diabetes and high risk of severe hypoglycaemia compared to insulin glargine is to be investigated.
Study design and intervention: A controlled, cross-over multi-centre study in a Prospective, Randomised, Open, Blinded Endpoint (PROBE) design. Each treatment period last for 12 months. Patients will be randomised to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order. Endpoints will be assessed during the last 9 months of each treatment arm.
Subjects: 175 type 1 diabetic patients with a history of one or more episodes of nocturnal severe hypoglycaemia during the proceeding two years.
Method: Patients will record all events of symptomatic (mild), asymptomatic (silent) and severe hypoglycaemia in a diary. All events of symptomatic nocturnal and severe hypoglycaemia must also be reported by telephone within 24 hours. Patients will be instructed to do and record self-monitored blood glucose (SMBG) i.e. 4-point profiles twice per week (blood glucose before breakfast, before lunch, before dinner and before bedtime).
Outcomes: See "Outcome Measures". Concerning the primary endpoint all possible symptomatic nocturnal hypoglycaemic episodes will be adjudicated by an independent endpoint committee consisting of diabetes specialists blinded to the individual patient insulin regimen.
Safety: Adverse reactions
- Being tested
- Insulin aspart/glargine, Insulin aspart/degludec
- Keywords
- Diabetes Mellitus, Hypoglycaemia, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Autoimmune Diseases, Insulin, Hypoglycaemic Agents, Physiological Effetcs of Drugs
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Autoimmune Diseases, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin aspart/glargineDrug
Also called NovoRapid, Lantus
Insulin aspart/degludecDrug
Also called NovoRapid, Tresiba
| Study group | Role | What they receive |
|---|---|---|
| Insulin glargine | Active comparator | Each treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance.
Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order.
After 12 months of treatment patients will cross-over to the other basal-bolus therapy.
Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals. Receives: Drug: Insulin aspart/glargine |
| Insulin degludec | Experimental | Each treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance.
Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order.
After 12 months of treatment patients will cross-over to the other basal-bolus therapy.
Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals. Receives: Drug: Insulin aspart/degludec |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptomatic nocturnal hypoglycaemia
Measured: 9 months (3-12) of each treatment period
Secondary outcomes (9)
Severe hypoglycaemia (total, night-time, daytime)
Measured: 9 months (3-12) of each treatment period
Any nocturnal hypoglycaemia (incl. asymptomatic/silent events)
Measured: 9 months (3-12) of each treatment period
Any daytime hypoglycaemia (symptomatic, asymptomatic/silent and severe)
Measured: 9 months (3-12) of each treatment period
Any CGM recorded hypoglycaemia (symptomatic, asymptomatic/silent and severe)
Measured: 2 x 6 days in each treatment arm
Any in-hospital nocturnal hypoglycaemia (incl. asymptomatic/silent events)
Measured: 2 overnight stays in each treatment arm
Change in HbA1c
Measured: From baseline to after 12 months of treatment
Change in glycaemic variability
Measured: 4 x overnight stays and 4 x 6 days of CGM
Insulin doses
Measured: End of each treatment period
Quality of life incl. pre-depression scale
Measured: At baseline, cross-over and after 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2014 (estimated)
- Study startJan 2015
- Primary completion28 Feb 2019
- Study completion28 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordsjaellands Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Steno Diabetes Center Copenhagen, Hvidovre University Hospital, Copenhagen University Hospital, Denmark, Zealand University Hospital, Odense University Hospital, Aarhus University Hospital, Esbjerg Hospital - University Hospital of Southern Denmark
- Responsible party
- Sponsor
- Investigators
- Ulrik Pedersen-Bjergaard, MD, DMSc, Principal investigator, Nordsjaellands Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02192450
- Sponsor's protocol ID
- HypoDeg
- Acronym
- HypoDeg
- Status last verified
- Jun 2019
- First submitted
- 9 Jul 2014
- Last updated
- 27 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brosen JMB, Agesen RM, Alibegovic AC, Andersen HU, Beck-Nielsen H, Gustenhoff P, Hansen TK, Hedetoft C, Jensen TJ, Juhl CB, Stolberg CR, Lerche SS, Norgaard K, Parving HH, Tarnow L, Thorsteinsson B, Pedersen-Bjergaard U. The Effect of Insulin Degludec Versus Insulin Glargine U100 on Glucose Metrics Recorded During Continuous Glucose Monitoring in People With Type 1 Diabetes and Recurrent Nocturnal Severe Hypoglycemia. J Diabetes Sci Technol. 2025 Mar;19(2):390-399. doi: 10.1177/19322968231197423. Epub 2023 Sep 6.
PubMed 37671755Brosen JMB, Agesen RM, Alibegovic AC, Ullits Andersen H, Beck-Nielsen H, Gustenhoff P, Krarup Hansen T, Hedetoft CGR, Jensen TJ, Stolberg CR, Bogh Juhl C, Lerche SS, Norgaard K, Parving HH, Tarnow L, Thorsteinsson B, Pedersen-Bjergaard U. Continuous Glucose Monitoring-Recorded Hypoglycemia with Insulin Degludec or Insulin Glargine U100 in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia. Diabetes Technol Ther. 2022 Sep;24(9):643-654. doi: 10.1089/dia.2021.0567. Epub 2022 Jun 22.
PubMed 35467938Agesen RM, Alibegovic AC, Andersen HU, Beck-Nielsen H, Gustenhoff P, Hansen TK, Hedetoft C, Jensen T, Juhl CB, Lerche SS, Norgaard K, Parving HH, Tarnow L, Thorsteinsson B, Pedersen-Bjergaard U. The effect of insulin degludec on risk of symptomatic nocturnal hypoglycaemia in adults with type 1 diabetes and high risk of nocturnal severe hypoglycaemia (the HypoDeg trial): study rationale and design. BMC Endocr Disord. 2019 Jul 23;19(1):78. doi: 10.1186/s12902-019-0408-x.
PubMed 31337371
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Insulin Degludec on Risk of Symptomatic Nocturnal Hypoglycaemia in Subjects With Type 1 Diabetes and High Risk of Nocturnal Severe Hypoglycaemia
- ClinicalTrials.gov ID
- NCT02192450
- Acronym / sponsor ID
- HypoDeg / HypoDeg
- Keywords
- Diabetes Mellitus, Hypoglycaemia, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Autoimmune Diseases, Insulin, Hypoglycaemic Agents
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Nordsjaellands HospitalUniversity, hospital or other
- Collaborators
- Steno Diabetes Center Copenhagen, Hvidovre University Hospital, Copenhagen University Hospital, Denmark, Zealand University Hospital, Odense University Hospital, Aarhus University Hospital, Esbjerg Hospital - University Hospital of Southern Denmark
- Study start
- Jan 2015
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 28 Feb 2019 (actual)
- First posted
- 16 Jul 2014 (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.
The purpose of this study is to determine whether insulin degludec compared to insulin glargine can reduce the risk of symptomatic nocturnal hypoglycaemia in subjects with the greatest potential benefit from optimised insulin treatment, which are patients with type 1 diabetes and high risk of nocturnal severe hypoglycaemia.
Detailed description
Background: Insulin degludec is a novel insulin analogue that may reduce the risk of mild nocturnal hypoglycaemia in type 1 diabetes. Patients with type 1 diabetes and recurrent severe hypoglycaemia (high risk patients) are also burdened by nocturnal hyoglycaemia (mild and silent). These episodes may contribute to the developement of hormonal counterregulatory failure and hypoglycaemia unawareness, which in turn increases the risk of further hypoglycaemic episodes, especially epiosdes of severe hypoglycaemia.The effect of insulin degludec on risk of mild nocturnal hypoglycaemia in subjects with type 1 diabetes and high risk of severe hypoglycaemia compared to insulin glargine is to be investigated.
Study design and intervention: A controlled, cross-over multi-centre study in a Prospective, Randomised, Open, Blinded Endpoint (PROBE) design. Each treatment period last for 12 months. Patients will be randomised to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order. Endpoints will be assessed during the last 9 months of each treatment arm.
Subjects: 175 type 1 diabetic patients with a history of one or more episodes of nocturnal severe hypoglycaemia during the proceeding two years.
Method: Patients will record all events of symptomatic (mild), asymptomatic (silent) and severe hypoglycaemia in a diary. All events of symptomatic nocturnal and severe hypoglycaemia must also be reported by telephone within 24 hours. Patients will be instructed to do and record self-monitored blood glucose (SMBG) i.e. 4-point profiles twice per week (blood glucose before breakfast, before lunch, before dinner and before bedtime).
Outcomes: See "Outcome Measures". Concerning the primary endpoint all possible symptomatic nocturnal hypoglycaemic episodes will be adjudicated by an independent endpoint committee consisting of diabetes specialists blinded to the individual patient insulin regimen.
Safety: Adverse reactions
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin glargine | Active comparator | Drug: Insulin aspart/glargineEach treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance. Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order. After 12 months of treatment patients will cross-over to the other basal-bolus therapy. Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals. |
| Insulin degludec | Experimental | Drug: Insulin aspart/degludecEach treatment arm last for 12 months - 3 months of run-in/cross-over and 9 months of maintenance. Patients will be randomised (1:1) to treatment with basal-bolus therapy with insulin aspart/degludec or insulin aspart/glargine in random order. After 12 months of treatment patients will cross-over to the other basal-bolus therapy. Insulin degludec and insulin glargine is administered once daily at the evening meal and insulin aspart is administered three times daily before the main meals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Type 1 diabetes > 5 years
- One or more episodes of nocturnal severe hypoglycaemia during the preceding two years
- Treated with multiple dose insulin injection (>2) or insulin pump. Both human insulin and insulin analogues are allowed
- Willingness to a once daily (OD) regimen concerning insulin degludec and insulin glargine
- Willingness to do self-monitoring of blood glucose (SMBG) and keep a diary
Key exclusion criteria (12 listed)
- History of primary and secondary adrenal insufficiency, growth hormone deficiency, or untreated myxoedema
- History of unstable angina or major cardiovascular events (myocardial infarction, coronary re-vascularisation, transient ischaemic attack, or stroke within the last three months)
- Heart failure, New York Heart Association (NYHA) class IV
- History of malignancy unless a disease-free period exceeding five years
- History of alcohol or drug abuse
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 |
|---|---|---|
| Insulin aspart/glargineAlso: NovoRapid, Lantus | Drug | Insulin glargine |
| Insulin aspart/degludecAlso: NovoRapid, Tresiba | Drug | Insulin degludec |
Primary outcome
Symptomatic nocturnal hypoglycaemia
Time frame: 9 months (3-12) of each treatment period
9 secondary outcomes
Severe hypoglycaemia (total, night-time, daytime)
Time frame: 9 months (3-12) of each treatment period
Any nocturnal hypoglycaemia (incl. asymptomatic/silent events)
Time frame: 9 months (3-12) of each treatment period
Any daytime hypoglycaemia (symptomatic, asymptomatic/silent and severe)
Time frame: 9 months (3-12) of each treatment period
Any CGM recorded hypoglycaemia (symptomatic, asymptomatic/silent and severe)
Time frame: 2 x 6 days in each treatment arm
Any in-hospital nocturnal hypoglycaemia (incl. asymptomatic/silent events)
Time frame: 2 overnight stays in each treatment arm
Change in HbA1c
Time frame: From baseline to after 12 months of treatment
Change in glycaemic variability
Time frame: 4 x overnight stays and 4 x 6 days of CGM
Insulin doses
Time frame: End of each treatment period
Quality of life incl. pre-depression scale
Time frame: At baseline, cross-over and after 24 months
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 27 Jun 2019.
- Derived from this study: PubMed 37671755Brosen JMB, Agesen RM, Alibegovic AC, Andersen HU, Beck-Nielsen H, Gustenhoff P, Hansen TK, Hedetoft C, Jensen TJ, Juhl CB, Stolberg CR, Lerche SS, Norgaard K, Parving HH, Tarnow L, Thorsteinsson B, Pedersen-Bjergaard U. The Effect of Insulin Degludec Versus Insulin Glargine U100 on Glucose Metrics Recorded During Continuous Glucose Monitoring in People With Type 1 Diabetes and Recurrent Nocturnal Severe Hypoglycemia. J Diabetes Sci Technol. 2025 Mar;19(2):390-399. doi: 10.1177/19322968231197423. Epub 2023 Sep 6.
- Derived from this study: PubMed 35467938Brosen JMB, Agesen RM, Alibegovic AC, Ullits Andersen H, Beck-Nielsen H, Gustenhoff P, Krarup Hansen T, Hedetoft CGR, Jensen TJ, Stolberg CR, Bogh Juhl C, Lerche SS, Norgaard K, Parving HH, Tarnow L, Thorsteinsson B, Pedersen-Bjergaard U. Continuous Glucose Monitoring-Recorded Hypoglycemia with Insulin Degludec or Insulin Glargine U100 in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia. Diabetes Technol Ther. 2022 Sep;24(9):643-654. doi: 10.1089/dia.2021.0567. Epub 2022 Jun 22.
- Derived from this study: PubMed 31337371Agesen RM, Alibegovic AC, Andersen HU, Beck-Nielsen H, Gustenhoff P, Hansen TK, Hedetoft C, Jensen T, Juhl CB, Lerche SS, Norgaard K, Parving HH, Tarnow L, Thorsteinsson B, Pedersen-Bjergaard U. The effect of insulin degludec on risk of symptomatic nocturnal hypoglycaemia in adults with type 1 diabetes and high risk of nocturnal severe hypoglycaemia (the HypoDeg trial): study rationale and design. BMC Endocr Disord. 2019 Jul 23;19(1):78. doi: 10.1186/s12902-019-0408-x.
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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.
Ulrik Pedersen-Bjergaard, MD, DMSc principal investigator
Nordsjaellands Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Insulin aspart/glargine and Insulin aspart/degludec in people with Type 1 Diabetes Mellitus and Nocturnal Hypoglycemia, run by Nordsjaellands Hospital at 1 site in Denmark.
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 12 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 27 Jun 2019. 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 Denmark. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Symptomatic nocturnal hypoglycaemia (time frame: 9 months (3-12) of each treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02192450, which also lists 3 linked publications.
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 27 Jun 2019.