Type 1 DiabetesNCT04800536
Cardiovascular Effects of Rapidly Declining Plasma Glucose in Patients With Type 1 Diabetes
A study testing Rapidly declining plasma glucose and Slowly declining plasma glucose in people with Type 1 Diabetes, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
Type 1 diabetes (T1D) is an autoimmune metabolic disease characterised by impaired lack of endogenous insulin causing elevated plasma glucose levels and increased risk of microvascular and macrovascular complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Rapidly declining plasma glucose and Slowly declining plasma glucose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jun 2021to 1 Apr 2023
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed and written consent
- Type 1 diabetes
- Age ≥18 years
- C-peptide negative (<0.2 nmol/l)
- Insulin treatment for ≥1 year
- HbA1C ≥63 mmol/mol
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- Informed and written consent
- Type 1 diabetes
- Age ≥18 years
- C-peptide negative (<0.2nmol/l)
- Insulin treatment for ≥1 year
- HbA1C ≤53 mmol/mol
Who cannot join
- Arrhythmia diagnosed prior to or at the time of the screening visit
- ECG with left or right bundle branch block diagnosed prior to the screening visit.
- Implantable cardioverter defibrillator or pacemaker at the time of inclusion
- Heart failure diagnosed prior to the screening visit (left ventricular ejection fraction < 45%)
- Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
- Thyroid dysfunction (except for well-regulated myxoedema)
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- Anaemia (male: haemoglobin <8.0 mmol/l; 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
Steno Diabetes Center Copenhagen - Gentofte Hospital
Copenhagen, 2900
About this study
Type 1 diabetes (T1D) is an autoimmune metabolic disease characterised by impaired lack of endogenous insulin causing elevated plasma glucose levels and increased risk of microvascular and macrovascular complications. With respect to the cardiovascular system, patients with T1D have an up to 10-fold increased risk of sudden cardiac death compared to healthy individuals. Furthermore, diabetes constitutes a hypercoagulable state, which to some extent may explain why cardiovascular disease still is a major cause of mortality in patients with T1D. Due to treatment with exogenously delivered insulin, glycaemic variability with intra-day and inter-day plasma glucose concentrations fluctuating between high levels (peaks) and low levels (nadirs), are inevitable in patients with T1D. A potentially important factor in development of cardiovascular disease, associated with glycaemic variability, is the rate of increase and/or decline of plasma glucose. The aim of this study is to test the hypothesis that a rapid plasma glucose decline from a hyperglycaemic level to an euglycaemic level can induce changes in QT-interval and blood coagulation in a proarrhythmogenic and prothrombotic way.
Twenty patients with T1D with a 1:1 distribution with chronic hyperglycaemia (HbA1C ≥63 mmol/mol) and with well-controlled diabetes (HbA1C ≤53 mmol/mol) will be recruited for a crossover study including two test days (protocols), P-rapid, a combined hyperglycaemic and euglycaemic clamp with rapidly declining plasma glucose and P-slow, a combined hyperglycaemic and euglycaemic clamp with slowly declining plasma glucose. Patients will be randomised 1:1 to start with P-rapid or P-slow. The cardiovascular effects will be investigated using Holter-ECG, Thrombelastography, Echocardiography and blood sampling.
Given that cardiovascular disease is a major cause of death in patients with T1D and that patients with diabetes may be more susceptible for cardiac arrhythmias and thrombotic events compared to healthy individuals, it is important to identify cardiovascular risk factors related to acute changes in plasma glucose in order to improve prevention strategies and therapy.
- Conditions
- Type 1 Diabetes
- Being tested
- Rapidly declining plasma glucose, Slowly declining plasma glucose
- Keywords
- Plasma glucose decline rate, Cardiovascular disease, Sudden cardiac death, Glycaemic variability
- Medical subject headings
- Diabetes Mellitus, Type 1, Cardiovascular Diseases, Death, Sudden, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rapidly declining plasma glucoseOther
Acute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Rapid plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l).
Slowly declining plasma glucoseOther
Acute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Slow plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l).
| Study group | Role | What they receive |
|---|---|---|
| Cardiovascular effects of rapidly declining plasma glucose | Experimental | A combined hyperglycaemic and euglycaemic clamp with a rapidly declining plasma glucose (>0.15 mmol/l/min). Plasma glucose will be measured every 5 minute and cardiovascular effects of the plasma glucose decline rate will be assessed using Holter-ECG, echocardiography, thrombelastography and blood sampling. Receives: Other: Rapidly declining plasma glucose |
| Cardiovascular effects of slowly declining plasma glucose | Experimental | A combined hyperglycaemic and euglycaemic clamp with slowly declining plasma glucose (<0.085 mmol/l/min). A combined hyperglycaemic and euglycaemic clamp with a slowly declining plasma glucose (>0.15 mmol/l/min). Plasma glucose will be measured every 5 minute and cardiovascular effects of the plasma glucose decline rate will be assessed using Holter-ECG, echocardiography, thrombelastography and blood sampling. Receives: Other: Slowly declining plasma glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
QTc interval
Difference in mean QTc (ms) interval from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Secondary outcomes (8)
Cardiac function
Difference in ventricular systolic function (measured by echocardiography) from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Heart rate variability
Difference in the sympathetic/parasympathetic balance (measured by heart rate variability) during a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Haemostatic balance
Difference in activation of coagulation and fibrinolysis (measured by TEG) from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Endothelial activation and damage
Difference in endothelial activation and damage (measured by Syndecan-1, Soluble thrombomodulin and sVE-cadherin) (ng/ml) from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Plasma glucose decline rate and counterregulatory hormonal response
Difference in counterregulatory hormonal response (plasma glucagon, catecholamines, cortisol, and growth hormone) from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Plasma glucose decline rate and oxidative stress
Difference in vascular oxidative stress (Tetrahydrobiopterin/dihydrobiopterin ratio, Dehydroascorbic acid/Ascorbic acid ratio, Asymmetric dimethylarginine/Arginine ratio, Malondialdehyde) from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Plasma glucose decline rate and potassium
Difference in plasma potassium concentration during a rapid plasma glucose decline compared to a slow plasma glucose decline from a hyperglycaemic level to an euglycaemic level.
Measured: 0-255 minutes
Plasma glucose decline rate and symptomatic response
Difference in symptomatic response (Edinburgh hypoglycaemia symptom scale) from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
Measured: 0-255 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2021
- Study start1 Jun 2021
- Primary completion16 Dec 2021
- Study completion1 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04800536
- Sponsor's protocol ID
- H-20033627
- Status last verified
- May 2022
- First submitted
- 4 Mar 2021
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Effects of Rapidly Declining Plasma Glucose in Patients With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04800536
- Acronym / sponsor ID
- H-20033627
- Conditions
- Type 1 Diabetes
- Keywords
- Plasma glucose decline rate, Cardiovascular disease, Sudden cardiac death, Glycaemic variability
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, Copenhagen University Hospital, Rigshospitalet
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 16 Dec 2021 (actual)
- Study completion
- 1 Apr 2023 (actual)
- First posted
- 16 Mar 2021 (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.
Type 1 diabetes (T1D) is an autoimmune metabolic disease characterised by impaired lack of endogenous insulin causing elevated plasma glucose levels and increased risk of microvascular and macrovascular complications. With respect to the cardiovascular system, patients with T1D have an up to 10-fold increased risk of sudden cardiac death compared to healthy individuals. Furthermore, diabetes constitutes a hypercoagulable state, which to some extent may explain why cardiovascular disease still is a major cause of mortality in patients with T1D. Due to treatment with exogenously delivered insulin, glycaemic variability with intra-day and inter-day plasma glucose concentrations fluctuating between high levels (peaks) and low levels (nadirs), are inevitable in patients with T1D. A potentially important factor in development of cardiovascular disease, associated with glycaemic variability, is the rate of increase and/or decline of plasma glucose. The aim of this study is to test the hypothesis that a rapid plasma glucose decline from a hyperglycaemic level to an euglycaemic level can induce changes in QT-interval and blood coagulation in a proarrhythmogenic and prothrombotic way.
Twenty patients with T1D with a 1:1 distribution with chronic hyperglycaemia (HbA1C ≥63 mmol/mol) and with well-controlled diabetes (HbA1C ≤53 mmol/mol) will be recruited for a crossover study including two test days (protocols), P-rapid, a combined hyperglycaemic and euglycaemic clamp with rapidly declining plasma glucose and P-slow, a combined hyperglycaemic and euglycaemic clamp with slowly declining plasma glucose. Patients will be randomised 1:1 to start with P-rapid or P-slow. The cardiovascular effects will be investigated using Holter-ECG, Thrombelastography, Echocardiography and blood sampling.
Given that cardiovascular disease is a major cause of death in patients with T1D and that patients with diabetes may be more susceptible for cardiac arrhythmias and thrombotic events compared to healthy individuals, it is important to identify cardiovascular risk factors related to acute changes in plasma glucose in order to improve prevention strategies and therapy.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cardiovascular effects of rapidly declining plasma glucose | Experimental | Other: Rapidly declining plasma glucoseA combined hyperglycaemic and euglycaemic clamp with a rapidly declining plasma glucose (>0.15 mmol/l/min). Plasma glucose will be measured every 5 minute and cardiovascular effects of the plasma glucose decline rate will be assessed using Holter-ECG, echocardiography, thrombelastography and blood sampling. |
| Cardiovascular effects of slowly declining plasma glucose | Experimental | Other: Slowly declining plasma glucoseA combined hyperglycaemic and euglycaemic clamp with slowly declining plasma glucose (<0.085 mmol/l/min). A combined hyperglycaemic and euglycaemic clamp with a slowly declining plasma glucose (>0.15 mmol/l/min). Plasma glucose will be measured every 5 minute and cardiovascular effects of the plasma glucose decline rate will be assessed using Holter-ECG, echocardiography, thrombelastography and blood sampling. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Informed and written consent
- Type 1 diabetes
- Age ≥18 years
- C-peptide negative (<0.2 nmol/l)
- Insulin treatment for ≥1 year
Key exclusion criteria (11 listed)
- Arrhythmia diagnosed prior to or at the time of the screening visit
- ECG with left or right bundle branch block diagnosed prior to the screening visit.
- Implantable cardioverter defibrillator or pacemaker at the time of inclusion
- Heart failure diagnosed prior to the screening visit (left ventricular ejection fraction < 45%)
- 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 |
|---|---|---|
| Rapidly declining plasma glucoseAcute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Rapid plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l). | Other | Cardiovascular effects of rapidly declining plasma glucose |
| Slowly declining plasma glucoseAcute plasma glucose decline, divided into the following three phases: 1) Hyperglycaemic phase (plasma glucose 15 mmol/l), 2) Slow plasma glucose decline phase and 3) Euglycaemic phase (plasma glucose 4.5-5.5 mmol/l). | Other | Cardiovascular effects of slowly declining plasma glucose |
Primary outcome
QTc interval
Time frame: 0-255 minutes
Difference in mean QTc (ms) interval from a hyperglycaemic level to an euglycaemic level preceded by a rapid plasma glucose decline compared to a slow plasma glucose decline in patients with T1D with chronic hyperglycaemia and well-controlled diabetes, respectively.
8 secondary outcomes
Cardiac function
Time frame: 0-255 minutes
Heart rate variability
Time frame: 0-255 minutes
Haemostatic balance
Time frame: 0-255 minutes
Endothelial activation and damage
Time frame: 0-255 minutes
Plasma glucose decline rate and counterregulatory hormonal response
Time frame: 0-255 minutes
Plasma glucose decline rate and oxidative stress
Time frame: 0-255 minutes
Plasma glucose decline rate and potassium
Time frame: 0-255 minutes
Plasma glucose decline rate and symptomatic response
Time frame: 0-255 minutes
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 12 Apr 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rapidly declining plasma glucose and Slowly declining plasma glucose in people with Type 1 Diabetes, 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 12 inclusion and 11 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 12 Apr 2024. 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?
QTc interval (time frame: 0-255 minutes). 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 12 Apr 2024.