Clinical trial NCT04011683: Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes
Official title: Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypoglycemia (Diabetic)
Hyperglycaemia (Diabetic)
Arrythmia, Cardiac
Type 1 Diabetes
Blood Glucose Fluctuations
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: University Hospital, Gentofte, Copenhagen
name: Hillerod Hospital, Denmark
First posted: 2019-07-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with type 1 Diabetes recrutted in collaboration with Hillerod hospital, Gentofte hospital and Steno Diabetes Centre.

Brief summary: The investigators hypothesise that patients with type 1 diabetes have clinically relevant, but often unrecognised, episodes of arrhythmias linked to episodes of hypoglycaemia and/or clinically significant fluctuations in plasma glucose.

Detailed description: 30 patients with type 1 diabetes will be recruited for a one-year observational study employing CGM (Continuous glucose monitor) and ILR (Implantable loop recorder). Patients will be scheduled for a three-week run-in period to ensure that the implanted ILR provides reliable data. Patient visits are planned for 0, 3, 6, 9, and 12 months and will include clinical examination, blood and urine samples, echocardiography (only first and last visit) and implant/explant of CGM. After 12 months, the participants will continue with an extended observation period of 2 years employing ILR and clinical examination.

Device: Loop recorder (Reveal LINQ, Medtronic, Minneapolis, MN, USA) Implantation of a loop-recorder

Device: Continuous glucose monitoring (Eversense XL, Senseonics, USA) Monitoring with a continuous glucose monitor

Eligibility criteria: Inclusion Criteria:

* Informed and written consent
* Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
* Age 18-80 years
* Fulfilling at least one of the below criteria\*:

  1. Recurrent hypoglycaemia (defined as \>1 episode/week with a plasma glucose measurement ≤3.9 mmol/l within the last 4 weeks)
  2. An episode of severe hypoglycaemia within the last year (according to the ADA definition, an event requiring assistance of another person to actively administer carbohydrates and/or glucagon, or take other corrective actions)
  3. Hypoglycaemic symptom unawareness (history of impaired autonomic response during hypoglycaemia)

(\*The aim is that all patients will fulfil criteria a or b. If the targeted sample size cannot be recruited, patients fulfilling criteria c will be included)

* Insulin treatment
* One or more clinical relevant complications to diabetes defined as\*\*:

  1. Nephropathy (creatinine \>130 μmol/l and/or microalbuminuria)
  2. Macrovascular disease defined as coronary disease (stable angina pectoris. previous unstable angina pectoris or myocardial infarction), cerebrovascular disease (previous stroke or transitional cerebral ischaemia), and peripheral vascular disease (previous intermittent claudication or prior acute ischemia)
  3. Peripheral neuropathy with vibration perception threshold of \>25 volt determined by biothesiometry
  4. Moderate to severe retinopathy
* Well-functioning ILR during run-in period (acceptable readings judged by an arrhythmologist)
* Participation in the extended study

(\*\*The aim is that all patients will fulfil criteria a or b. If the targeted sample size cannot be recruited, patients fulfilling criteria c or d will be included)

Exclusion Criteria:

* Arrhythmia diagnosed prior to the screening visit
* ICD or pacemaker at the time of inclusion
* Severe heart failure (left ventricular ejection fraction \<25%)
* Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
* Thyroid dysfunction (except for well-regulated eltroxine substituted myxoedema)

Primary outcomes:
measure: Incidence of cardiac arrhythmias during hypoglycaemia, euglycaemia, hyperglycaemia.
timeFrame: Within 12 months
Secondary outcomes:
measure: Prevalence of cardiac arrhythmias
timeFrame: Within 12 months
measure: Cardiac arrhythmias during LGV, HGV.
timeFrame: Within 12 months
measure: The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
timeFrame: Within 12 months
measure: The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
timeFrame: Within 12 months
measure: The relationship between diabetes complication status at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
timeFrame: Within 12 months
measure: Hypoglycaemia and cardiac arrhythmia
timeFrame: Within 12 months
measure: Plasma glucose variation and cardiac arrhythmias
timeFrame: Within 12 months
measure: CV, SD, ADRR, LBGI, HBGI, CONGA-1 and cardiac arrhythmias
timeFrame: Within 12 months
measure: Mean amplitude of glycaemic excursions (MAGE) and cardiac arrhythmia.
timeFrame: Within 12 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Clinical Metabolic Physiology, SDCC
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Tina Vilsbøll, MD, Professor
role: STUDY_DIRECTOR
References: