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

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ClinicalTrials.gov Identifier: NCT03956173
Recruitment Status : Active, not recruiting
First Posted : May 20, 2019
Last Update Posted : June 18, 2019
Sponsor:
Collaborators:
University Hospital, Gentofte, Copenhagen
Hillerod Hospital, Denmark
Information provided by (Responsible Party):
Steno Diabetes Center Copenhagen

Brief Summary:
The investigators hypothesise that following episodes of hypoglycaemia, rebound hyperglycaemia may result in a prolonged period of increased QTc and, thereby, increased susceptibility to serious cardiac arrhythmias in patients with type - 1 diabetes.

Condition or disease Intervention/treatment
Diabetes type1 Hypoglycemia Arrhythmias, Cardiac Other: Hypoglycemic combined with either normo or hyperglycemic clamp.

Detailed Description:
In this study, changes in cardiac rhythm, haemodynamic regulation, and hormonal response will be evaluated during insulin-induced hypoglycaemia followed by hyperglycaemia and euglycaemia, respectively, on two separate experimental days. Twenty-four patients with type-1 diabetes are included. Patients are randomised 1:1 to start with either the combined hypo- and hyperglycaemic or the hypo- and euglycaemic clamp. After an overnight 10 hour fast, participants are admitted for a 255 minute clamp. An individualised insulin infusion will be initiated targeting a plasma glucose level of 5.0-8.0 mmol/l. When the targeted plasma glucose level is achieved, the hyperinsulinaemic euglycaemic clamp will be initiated at time 0. The insulin infusion will be fixed at an infusion rate 80 mU/m2/min and a 20% glucose infusion will be initiated in order to regulate plasma glucose levels. After 45 min of monitoring at euglycaemic plasma glucose level, plasma glucose will be decreased over a period of 30 minutes, targeting 2.5 mmol/l for a period of 60 min in a hyperinsulinaemic hypoglycaemic clamp. From 135 min to 195 min, plasma glucose levels will be increased to either hyperglycaemic level (20mmol/l) or normoglycaemic (6mmol/L) and will be kept constant for 105 minutes. Echocardiography is performed at baseline, at hypoglycaemic level and at hyper-or normoglycaemic level. Blood samples are taken every 15 minutes throughout the entire clamp, however bedside plasma glucose is analysed every fifth minute. A Holter-ECG is obtained throughout the entire clamp.

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Study Type : Observational
Estimated Enrollment : 24 participants
Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Clamp group
24 patients with type 1 diabetes.
Other: Hypoglycemic combined with either normo or hyperglycemic clamp.
Twenty-four patients with type 1 diabetes has been recruited for a cross-over study including two experimental days, a combined hypo- and hyperlycemic clamp and a combined hypo- and euglycemic clamp, respectively. Patients will be randomised 1:1 to start with either the combined hypo- and hyperglycemic or the hypo- and euglycemic clamp. The hypo- and hyperglycemic or the hypo- and euglycemic clamp are estimated to last 255 minutes. The two clamp days will be separated by at least 30 days.




Primary Outcome Measures :
  1. QTc prolongation. [ Time Frame: 255 minutes ]
    Difference in mean corrected QT interval (QTc) prolongation during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia


Secondary Outcome Measures :
  1. QTd dispersion. [ Time Frame: 255 minutes ]
    Difference in QT dispersion (QTd) during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia

  2. Atrial ectopic beats. [ Time Frame: 255 minutes ]
    Difference in atrial ectopic beats (prematurity threshold 30%),during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia

  3. Bradycardia [ Time Frame: 255 minutes ]
    Difference in non-clinically significant bradycardia (≤45 bpm for 5 seconds) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia

  4. Ventricular premature beats [ Time Frame: 255 minutes ]
    Difference in ventricular premature beats during hyperglycaemia compared to euglycaemia both preceded by insulin-induced hypoglycaemia

  5. Glucagon response [ Time Frame: 255 minutes ]
    Differences in glucagon response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia

  6. Catecholamine response [ Time Frame: 255 minutes ]
    Differences in catecholamine response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia

  7. Growth hormone response [ Time Frame: 255 minutes ]
    Differences in growth hormone response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia

  8. Cortisol response [ Time Frame: 255 minutes ]
    Differences in cortisol responses during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia

  9. Haemodynamic regulation. [ Time Frame: 255 minutes ]
    Differences in haemodynamic regulation (measured by echocardiography) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia

  10. Inflammatory response [ Time Frame: 255 minutes ]
    Differences in markers of inflammation (high-sensitive C-reactive peptide (hs-CRP) and interleukin 6 (IL-6)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia

  11. Oxidative stress markers (8-iso-PGF2α) [ Time Frame: 255 minutes ]
    Differences in markers of oxidative stress (8-iso prostaglandin F2α (8-iso-PGF2α)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia

  12. Oxidative stress markers (8-oxoGuo) [ Time Frame: 255 minutes ]
    Differences in markers of oxidative stress (8-oxo-7,8-dihydroguanosine (8-oxoGuo)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia



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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
24 patients with type 1 diabetes with insulin treatment for ≥ 3 years.
Criteria

Inclusion Criteria:

  • Informed and written consent
  • Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
  • Age 18-70 years
  • Insulin treatment for ≥3 years

Exclusion Criteria:

  • Arrhythmia diagnosed prior to the screening visit
  • Implantable cardioverter defibrillator (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 eltroxin substituted myxoedema)
  • Anaemia (male: haemoglobin <8.0; female: haemoglobin <7.0 mmol/l)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03956173


Locations
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Denmark
Clinical Metabolic Physiology, SDCC
Copenhagen, Denmark, 2900
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
University Hospital, Gentofte, Copenhagen
Hillerod Hospital, Denmark
Investigators
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Study Director: Tina Vilsbøll, MD,Professor Steno diabetic centre (SDCC)

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Responsible Party: Steno Diabetes Center Copenhagen
ClinicalTrials.gov Identifier: NCT03956173     History of Changes
Other Study ID Numbers: H-18034040
First Posted: May 20, 2019    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Hypoglycemia
Diabetes Mellitus
Arrhythmias, Cardiac
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Hypoglycemic Agents
Physiological Effects of Drugs