Clinical trial NCT02192450: Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Nocturnal Hypoglycemia
Recurrent Severe Hypoglycaemia
Keywords: Diabetes Mellitus
Hypoglycaemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Insulin
Hypoglycaemic Agents
Physiological Effetcs of Drugs
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
Collaborators: name: Steno Diabetes Center Copenhagen
name: Hvidovre University Hospital
name: Copenhagen University Hospital, Denmark
name: Zealand University Hospital
name: Odense University Hospital
name: Aarhus University Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
First posted: 2014-07-16
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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 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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Symptomatic nocturnal hypoglycaemia
timeFrame: 9 months (3-12) of each treatment period
Secondary outcomes:
measure: Severe hypoglycaemia (total, night-time, daytime)
timeFrame: 9 months (3-12) of each treatment period
measure: Any nocturnal hypoglycaemia (incl. asymptomatic/silent events)
timeFrame: 9 months (3-12) of each treatment period
measure: Any daytime hypoglycaemia (symptomatic, asymptomatic/silent and severe)
timeFrame: 9 months (3-12) of each treatment period
measure: Any CGM recorded hypoglycaemia (symptomatic, asymptomatic/silent and severe)
timeFrame: 2 x 6 days in each treatment arm
measure: Any in-hospital nocturnal hypoglycaemia (incl. asymptomatic/silent events)
timeFrame: 2 overnight stays in each treatment arm
measure: Change in HbA1c
timeFrame: From baseline to after 12 months of treatment
measure: Change in glycaemic variability
timeFrame: 4 x overnight stays and 4 x 6 days of CGM
measure: Insulin doses
timeFrame: End of each treatment period
measure: Quality of life incl. pre-depression scale
timeFrame: At baseline, cross-over and after 24 months
Other outcomes:
Locations:
city: Hilleroed
country: Denmark
facility: Nordsjaellands Hospital
Study officials:
affiliation: Nordsjaellands Hospital
name: Ulrik Pedersen-Bjergaard, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brosen 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.
citation: Agesen 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.