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出境医 / 临床实验 / Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes (Hypo-Heart-1)

Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes (Hypo-Heart-1)

Study Description
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.

Condition or disease
Hypoglycemia (Diabetic) Hyperglycaemia (Diabetic) Arrythmia, Cardiac Type 1 Diabetes Blood Glucose Fluctuations

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

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 1, 2021
Arms and Interventions
Outcome Measures
Primary Outcome Measures :
  1. Incidence of cardiac arrhythmias during hypoglycaemia, euglycaemia, hyperglycaemia. [ Time Frame: Within 12 months ]
    Incidence of clinically relevant arrhythmias during hypoglycaemia (plasma glucose ≤3.9 mmol/l) compared to euglycaemia and hyperglycaemia.


Secondary Outcome Measures :
  1. Prevalence of cardiac arrhythmias [ Time Frame: Within 12 months ]
    Prevalence of clinically relevant arrhythmias

  2. Cardiac arrhythmias during LGV, HGV. [ Time Frame: Within 12 months ]
    Clinical relevant arrhythmias during low glucose variability (LGV), defined as variations in plasma glucose below or equal to 5 mmol/l within two hours preceding an arrhythmic event, compared to high glucose variability (HGV), defined as variations in plasma glucose above 5 mmol/l within two hours preceding an arrhythmic event.

  3. The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV [ Time Frame: Within 12 months ]
    The relationship between cardiovascular disease (heart failure and ischaemic heart disease) at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV

  4. The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV [ Time Frame: Within 12 months ]
    The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV

  5. The relationship between diabetes complication status at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV [ Time Frame: Within 12 months ]
    The relationship between diabetes complication status (neuropathy, nephropathy, retinopathy) at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV

  6. Hypoglycaemia and cardiac arrhythmia [ Time Frame: Within 12 months ]
    The correlation between prevalence and total duration of hypoglycaemia and risk of clinically relevant arrhythmias

  7. Plasma glucose variation and cardiac arrhythmias [ Time Frame: Within 12 months ]
    The correlation between plasma glucose variation (variation in plasma glucose (Δ mmol/l) within two hours of the event) and risk of clinically relevant arrhythmias

  8. CV, SD, ADRR, LBGI, HBGI, CONGA-1 and cardiac arrhythmias [ Time Frame: Within 12 months ]
    The correlation between measures of glycaemic variability (coefficient of variation (CV), standard deviation (SD), average daily risk range (ADRR), low blood glucose index (LBGI), high blood glucose index (HBGI) and continuous overlapping net glycaemic action (CONGA-1)) and risk of clinically relevant arrhythmias

  9. Mean amplitude of glycaemic excursions (MAGE) and cardiac arrhythmia. [ Time Frame: Within 12 months ]
    Difference in mean amplitude of glycaemic excursions (MAGE) two hours preceding an arrhythmic event versus MAGE during non-event


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with type 1 Diabetes recrutted in collaboration with Hillerod hospital, Gentofte hospital and Steno Diabetes Centre.
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)
Contacts and Locations

Contacts
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Contact: Per Hagelqvist, MD +4531390346 per.gustav.hagelqvist.01@regionh.dk
Contact: Christine Rode Andreasen, MD, PHD christine.rode.andreasen.01@regionh.dk

Locations
Layout table for location information
Denmark
Clinical Metabolic Physiology, SDCC Recruiting
Copenhagen, Denmark, 2900
Contact: Bente Petersen    +4530694005    bente.petersen.03@regionh.dk   
Sub-Investigator: Per Hagelqvist, MD         
Sub-Investigator: Christine Rode Andreasen, MD         
Principal Investigator: Tina Vilsbøll, MD, DMSc         
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
University of Copenhagen
University Hospital, Gentofte, Copenhagen
Hillerod Hospital, Denmark
Investigators
Layout table for investigator information
Study Director: Tina Vilsbøll, MD, Professor Steno Diabetes Center Copenhagen
Tracking Information
First Submitted Date June 17, 2019
First Posted Date July 8, 2019
Last Update Posted Date November 20, 2020
Actual Study Start Date December 1, 2018
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 5, 2019)
Incidence of cardiac arrhythmias during hypoglycaemia, euglycaemia, hyperglycaemia. [ Time Frame: Within 12 months ]
Incidence of clinically relevant arrhythmias during hypoglycaemia (plasma glucose ≤3.9 mmol/l) compared to euglycaemia and hyperglycaemia.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 5, 2019)
  • Prevalence of cardiac arrhythmias [ Time Frame: Within 12 months ]
    Prevalence of clinically relevant arrhythmias
  • Cardiac arrhythmias during LGV, HGV. [ Time Frame: Within 12 months ]
    Clinical relevant arrhythmias during low glucose variability (LGV), defined as variations in plasma glucose below or equal to 5 mmol/l within two hours preceding an arrhythmic event, compared to high glucose variability (HGV), defined as variations in plasma glucose above 5 mmol/l within two hours preceding an arrhythmic event.
  • The relationship between cardiovascular disease at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV [ Time Frame: Within 12 months ]
    The relationship between cardiovascular disease (heart failure and ischaemic heart disease) at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
  • The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV [ Time Frame: Within 12 months ]
    The relationship between pharmacological treatment at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
  • The relationship between diabetes complication status at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV [ Time Frame: Within 12 months ]
    The relationship between diabetes complication status (neuropathy, nephropathy, retinopathy) at baseline and clinically relevant arrhythmias in relation to hypoglycaemia and HGV
  • Hypoglycaemia and cardiac arrhythmia [ Time Frame: Within 12 months ]
    The correlation between prevalence and total duration of hypoglycaemia and risk of clinically relevant arrhythmias
  • Plasma glucose variation and cardiac arrhythmias [ Time Frame: Within 12 months ]
    The correlation between plasma glucose variation (variation in plasma glucose (Δ mmol/l) within two hours of the event) and risk of clinically relevant arrhythmias
  • CV, SD, ADRR, LBGI, HBGI, CONGA-1 and cardiac arrhythmias [ Time Frame: Within 12 months ]
    The correlation between measures of glycaemic variability (coefficient of variation (CV), standard deviation (SD), average daily risk range (ADRR), low blood glucose index (LBGI), high blood glucose index (HBGI) and continuous overlapping net glycaemic action (CONGA-1)) and risk of clinically relevant arrhythmias
  • Mean amplitude of glycaemic excursions (MAGE) and cardiac arrhythmia. [ Time Frame: Within 12 months ]
    Difference in mean amplitude of glycaemic excursions (MAGE) two hours preceding an arrhythmic event versus MAGE during non-event
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes
Official Title Hypoglycaemia and Cardiac Arrhythmias in Type 1 Diabetes
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

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients with type 1 Diabetes recrutted in collaboration with Hillerod hospital, Gentofte hospital and Steno Diabetes Centre.
Condition
  • Hypoglycemia (Diabetic)
  • Hyperglycaemia (Diabetic)
  • Arrythmia, Cardiac
  • Type 1 Diabetes
  • Blood Glucose Fluctuations
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 5, 2019)
30
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 1, 2021
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
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)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Per Hagelqvist, MD +4531390346 per.gustav.hagelqvist.01@regionh.dk
Contact: Christine Rode Andreasen, MD, PHD christine.rode.andreasen.01@regionh.dk
Listed Location Countries Denmark
Removed Location Countries  
 
Administrative Information
NCT Number NCT04011683
Other Study ID Numbers H-18034040_part2
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Steno Diabetes Center Copenhagen
Study Sponsor Steno Diabetes Center Copenhagen
Collaborators
  • University of Copenhagen
  • University Hospital, Gentofte, Copenhagen
  • Hillerod Hospital, Denmark
Investigators
Study Director: Tina Vilsbøll, MD, Professor Steno Diabetes Center Copenhagen
PRS Account Steno Diabetes Center Copenhagen
Verification Date November 2020