Diabetes Mellitus, Type 1NCT04650646
Cardiovascular Effects of Exercise-related Hypoglycaemia in Patients With Type 1 Diabetes (Hypo Heart Exercise)
A study testing Exercise-related hypoglycaemia and Hypoglycaemia under resting conditions in people with Diabetes Mellitus, Type 1 and Arrhythmia, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1, Arrhythmia
- What is being tested?
- Exercise-related hypoglycaemia and Hypoglycaemia under resting conditions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2020to 1 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Clinical Research, Steno Diabetes Center Copenhagen-Gentofte
Copenhagen, 2900
About this study
Official title: Cardiovascular Effects of Exercise-related Hypoglycaemia in Patients With Type 1 Diabetes
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.
- Conditions
- Diabetes Mellitus, Type 1, Arrhythmia
- Being tested
- Exercise-related hypoglycaemia, Hypoglycaemia under resting conditions
- Keywords
- Type 1 diabetes, Cardiovascular disease, Hypoglycaemia, Exercise-related hypoglycaemia
- Medical subject headings
- Diabetes Mellitus, Type 1, Arrhythmias, Cardiac, Cardiovascular Diseases, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise-related hypoglycaemiaOther
Hypoglycaemia induced by intravenous insulin and exercise on a vertical cycle ergometer.
Hypoglycaemia under resting conditionsOther
Hypoglycaemia induced by intravenous insulin during bed rest.
| Study group | Role | What they receive |
|---|---|---|
| Hypoglycaemic clamp i combination with exercise | Experimental | A 180 minutes hyperinsulinaemic euglycaemic-hypoglycaemic clamp in combination with an exercise session. The participants will be monitored with Holter-ECG throughout the entire clamp and plasma glucose will be measured every 5 minutes. Blood samples will be drawn and analysed for changes in electrolytes, counterregulatory hormones, coagulation status, inflammation, endothelial damage and oxidative stress. Receives: Other: Exercise-related hypoglycaemia |
| Hypoglycaemic clamp in combination with bed rest | Experimental | A 180 minutes hyperinsulinaemic euglycaemic-hypoglycaemic clamp in combination with bed rest. The participants will be monitored with Holter-ECG throughout the entire clamp and plasma glucose will be measured every 5 minutes. Blood samples will be drawn and analysed for changes in electrolytes, counterregulatory hormones, coagulation status, inflammation, endothelial damage and oxidative stress. Receives: Other: Hypoglycaemia under resting conditions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypoglycaemia and QTc interval prolongation
Mean QTc interval prolongation from baseline during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.
Measured: 0-180minutes
Secondary outcomes (13)
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.
Measured: 0-24hours
Hypoglycaemia and QT dispersion (QTd)
Differences in QTd, during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions
Measured: 0-180minutes
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.
Measured: 0-180minutes
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.
Measured: 0-180minutes
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.
Measured: 0-180minutes
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.
Measured: 0-24hours
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.
Measured: 0-24hours
Hypoglycaemia and electrolytes
Differences in electrolyte concentrations including potassium and ionised calcium during exercise-related hypoglycaemia compared insulin-induced hypoglycaemia under resting conditions.
Measured: 0-180minutes
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.
Measured: 0-180minutes
Hypoglycaemia and markers of inflammation
Differences in inflammatory response (including interleukin 6 and TNFα) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.
Measured: 0-24hours
Hypoglycaemia and inflammation
Differences in High-sensitive C-reactive peptide (HsCRP) during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.
Measured: 0-24hours
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.
Measured: 0-180min
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.
Measured: 0minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2020
- Study start1 Sep 2020
- Primary completion3 Jun 2021
- Study completion1 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tina Vilsbøll, Steno Diabetes Center Copenhagen
- Investigators
- Tina Vilsbøll, MD, DMSc, Principal investigator, Steno diabetic centre (SDCC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04650646
- Sponsor's protocol ID
- H-20023688
- Status last verified
- Jan 2022
- First submitted
- 12 Nov 2020
- Last updated
- 21 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Effects of Exercise-related Hypoglycaemia in Patients With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04650646
- Acronym / sponsor ID
- H-20023688
- Conditions
- Diabetes Mellitus, Type 1, Arrhythmia
- Keywords
- Type 1 diabetes, Cardiovascular disease, Hypoglycaemia, Exercise-related hypoglycaemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 3 Jun 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 2 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoglycaemic clamp i combination with exercise | Experimental | Other: Exercise-related hypoglycaemiaA 180 minutes hyperinsulinaemic euglycaemic-hypoglycaemic clamp in combination with an exercise session. The participants will be monitored with Holter-ECG throughout the entire clamp and plasma glucose will be measured every 5 minutes. Blood samples will be drawn and analysed for changes in electrolytes, counterregulatory hormones, coagulation status, inflammation, endothelial damage and oxidative stress. |
| Hypoglycaemic clamp in combination with bed rest | Experimental | Other: Hypoglycaemia under resting conditionsA 180 minutes hyperinsulinaemic euglycaemic-hypoglycaemic clamp in combination with bed rest. The participants will be monitored with Holter-ECG throughout the entire clamp and plasma glucose will be measured every 5 minutes. Blood samples will be drawn and analysed for changes in electrolytes, counterregulatory hormones, coagulation status, inflammation, endothelial damage and oxidative stress. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise-related hypoglycaemiaHypoglycaemia induced by intravenous insulin and exercise on a vertical cycle ergometer. | Other | Hypoglycaemic clamp i combination with exercise |
| Hypoglycaemia under resting conditionsHypoglycaemia induced by intravenous insulin during bed rest. | Other | Hypoglycaemic clamp in combination with bed rest |
Primary outcome
Hypoglycaemia and QTc interval prolongation
Time frame: 0-180minutes
Mean QTc interval prolongation from baseline during exercise-related hypoglycaemia compared to insulin-induced hypoglycaemia under resting conditions.
13 secondary outcomes
Key secondary outcome: Hypoglycaemia and coagulation and fibrinolysis
Time frame: 0-24hours
Hypoglycaemia and QT dispersion (QTd)
Time frame: 0-180minutes
Hypoglycaemia and heart rate variability (HRV)
Time frame: 0-180minutes
Hypoglycaemia and bradycardia
Time frame: 0-180minutes
Hypoglycaemia and ectopic beats
Time frame: 0-180minutes
Hypoglycaemia and endothelial activation and damage
Time frame: 0-24hours
Hypoglycaemia and vascular oxidative stress
Time frame: 0-24hours
Hypoglycaemia and electrolytes
Time frame: 0-180minutes
Hypoglycaemia and counterregulatory hormonal response
Time frame: 0-180minutes
Hypoglycaemia and markers of inflammation
Time frame: 0-24hours
Hypoglycaemia and inflammation
Time frame: 0-24hours
Hypoglycaemia and continuous glucose monitoring (CGM) accuracy
Time frame: 0-180min
Type 1 diabetes, healthy controls and coagulability
Time frame: 0minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tina Vilsbøll, MD, DMSc principal investigator
Steno diabetic centre (SDCC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise-related hypoglycaemia and Hypoglycaemia under resting conditions in people with Diabetes Mellitus, Type 1 and Arrhythmia, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hypoglycaemia and QTc interval prolongation (time frame: 0-180minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2022.