Cardiovascular Effects of Exercise-related Hypoglycaemia in Patients With Type 1 Diabetes (Hypo Heart Exercise)

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

Cardiovascular Effects of Exercise-related Hypoglycaemia in Patients With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04650646
• Other study ID #: H-20023688
• Status: Completed
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: December 1, 2021

Study information

• Verified date: January 2022
• Source: Steno Diabetes Center Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with type 1 diabetes are recommended to perform at least 150 minutes of accumulated physical activity each week, however fear of hypoglycaemia is a well-known barrier to exercise in these patients. Previous experimental studies have almost exclusively focused on investigating cardiovascular effects of hypoglycaemia under resting conditions, however other underlying circumstances prior to or during a hypoglycaemic event, (e.g. exercise) are rarely discussed in the literature but might, nevertheless, be of significant clinical importance.

In this study, the investigators aim to investigate the QT interval dynamics and prothrombotic factors during exercise-related hypoglycaemia in comparison with hypoglycaemia under resting conditions, in patients with type 1 diabetes.

Fifteen patients with type 1 diabetes will be recruited for a crossover study including two test days, a combined euglycaemic- hypoglycaemic clamp combined with an exercise session and an euglycaemic- hypoglycaemic clamp during bed rest, respectively. Furthermore, the participants will be schedueled for a 24-hours followup visit after each test day for the purpose of investigating prolonged prothrombotic effects of hypoglycaemia. Patients will be randomised 1:1 to start with the combined exercise-clamp or the resting-clamp. The two test days will be separated by at least 4 weeks to minimise carry-over effects. A group of fifteen healthy individuals with normal glucose tolerance matched for age, gender and body mass index, will be recruited for a single blood test aiming to compare baseline coagulation status with patients with type 1 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 1, 2021
• Est. primary completion date: June 3, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed and written consent

• Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)

• Age = 18 years

• Insulin treatment for =1 year

Exclusion Criteria:

• Arrhythmia diagnosed prior to the screening visit.

• Ischaemic heart disease or myocardial infarction diagnosed prior to the screening visit.

• Implantable cardioverter defibrillator (ICD) or pacemaker at the time of inclusion

• Heart failure (left ventricular ejection fraction <45%) diagnosed prior to the screening visit.

• Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)

• ECG with left or right bundle branch block diagnosed prior to the screening visit.

• Thyroid dysfunction (except for well-regulated levothyroxine-substituted myxoedema)

• Anaemia (male: haemoglobin <8.0; female: haemoglobin <7.0 mmol/l)

• Treatment with anticoagulant or antiplatelet treatment.

• Bleeding disorder diagnosed prior to the screening visit.

Withdrawal criteria

• The participants may withdraw at will at any time

Related Conditions & MeSH terms

• Arrhythmia
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Other:
• Exercise-related hypoglycaemia
Hypoglycaemia induced by intravenous insulin and exercise on a vertical cycle ergometer.
• Hypoglycaemia under resting conditions
Hypoglycaemia induced by intravenous insulin during bed rest.

Locations

Country	Name	City	State
Denmark	Clinical Research, Steno Diabetes Center Copenhagen-Gentofte	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hypoglycaemia and QTc interval prolongation	Mean QTc interval prolongation from baseline during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-180minutes
Secondary	Key secondary outcome: Hypoglycaemia and coagulation and fibrinolysis	Differences in whole blood coagulability and fibrinolysis (measured by thrombelastography) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-24hours
Secondary	Hypoglycaemia and QT dispersion (QTd)	Differences in QTd, during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions	0-180minutes
Secondary	Hypoglycaemia and heart rate variability (HRV)	Changes in sympathetic/parasympathetic balance (measured by HRV) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-180minutes
Secondary	Hypoglycaemia and bradycardia	Differences in non-clinically significant bradycardia (=45 bpm for 5 seconds) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-180minutes
Secondary	Hypoglycaemia and ectopic beats	Differences in number of atrial ectopic beats (prematurity threshold 30%) and ventricular premature beats respectively, during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-180minutes
Secondary	Hypoglycaemia and endothelial activation and damage	Differences in plasma markers of endothelial activation and damage (ng/ml) (including Syndecan-1, Soluble thrombomodulin and PECAM-1) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-24hours
Secondary	Hypoglycaemia and vascular oxidative stress	Differences in markers of vascular oxidative stress (tetrahydrobiopterin/dihydrobiopterin ratio, dehydroascorbic acid/ascorbic acid ratio, asymmetric dimethylarginine/arginine ratio, malondialdehyde) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-24hours
Secondary	Hypoglycaemia and electrolytes	Differences in electrolyte concentrations including potassium and ionised calcium during exercise-related hypoglycaemia compared insulin-induced hypoglycaemia under resting conditions.	0-180minutes
Secondary	Hypoglycaemia and counterregulatory hormonal response	Differences in hormonal response (plasma glucagon, cortisol, catecholamines and growth hormone) during exercise-related hypoglycaemia compared insulin-induced hypoglycaemia under resting conditions.	0-180minutes
Secondary	Hypoglycaemia and markers of inflammation	Differences in inflammatory response (including interleukin 6 and TNFa) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-24hours
Secondary	Hypoglycaemia and inflammation	Differences in High-sensitive C-reactive peptide (HsCRP) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.	0-24hours
Secondary	Hypoglycaemia and continuous glucose monitoring (CGM) accuracy	Differences in mean absolute relative difference (MARD) between Dexcom G6®, Abbot Flash Libre® and Yellow Springs Instrument (YSI) reference throughout both experimental days.	0-180min
Secondary	Type 1 diabetes, healthy controls and coagulability	Differences in whole blood coagulability and fibrinolysis (measured by thrombelastography) between patients with type 1 diabetes and healthy control subjects.	0minutes