Diabetes type1Hypo-Heart-1NCT03956173
Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes
An observational study of Diabetes type1 and Hypoglycemia, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
The investigators hypothesise that following episodes of hypoglycemia, rebound hyperglycemia may result in a prolonged period of increased QTc and, thereby, increased susceptibility to serious cardiac arrhythmias in patients with type - 1 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetes type1, Hypoglycemia, Arrhythmias, Cardiac
- What is being tested?
- Hypoglycemic combined with either normo or hyperglycemic clamp.
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Dec 2018to 1 Dec 2021
- Phase
- Observational
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 24 patients with type 1 diabetes with insulin treatment for ≥ 3 years.
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 18-70 years
- Insulin treatment for ≥3 years
Who cannot join
- 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)
- Anemia (male: hemoglobin <8.0; female: hemoglobin <7.0 mmol/l)
Trial locations and contacts
1 site in 1 country.
About this study
The investigators hypothesise that following episodes of hypoglycemia, rebound hyperglycemia may result in a prolonged period of increased QTc and, thereby, increased susceptibility to serious cardiac arrhythmias in patients with type - 1 diabetes.
Read the detailed description
In this study, changes in cardiac rhythm, haemodynamic regulation, and hormonal response will be evaluated during insulin-induced hypoglycemia followed by hyperglycemia and euglycemia, 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 hyperglycemic or the hypo- and euglycemic 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 hyperinsulinemic euglycemic 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 euglycemic 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 hyperinsulinemic hypoglycemic clamp. From 135 min to 195 min, plasma glucose levels will be increased to either hyperglycemic level or euglycemic level and will be kept constant for 105 minutes. Echocardiography is performed at baseline, at hypoglycemic level and at hyper-or normoglycemic 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.
- Conditions
- Diabetes type1, Hypoglycemia, Arrhythmias, Cardiac
- Being tested
- Hypoglycemic combined with either normo or hyperglycemic clamp.
- Medical subject headings
- Hypoglycemia, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoglycemic combined with either normo or hyperglycemic clamp.Other
Twenty-four patients with type 1 diabetes has been recruited for a cross-over study including two experimental days, a combined hypo- and hyperglyemic 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.
| Study group | Role | What they receive |
|---|---|---|
| Clamp group | 24 patients with type 1 diabetes. Receives: Other: Hypoglycemic combined with either normo or hyperglycemic clamp. |
What is being measured
The primary outcome is the main question the study is designed to answer.
QTc prolongation.
Difference in mean corrected QT interval (QTc) prolongation during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
Measured: 255 minutes
Secondary outcomes (12)
QTd dispersion.
Difference in QT dispersion (QTd) during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
Measured: 255 minutes
Atrial ectopic beats.
Difference in atrial ectopic beats (prematurity threshold 30%),during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia
Measured: 255 minutes
Bradycardia
Difference in non-clinically significant bradycardia (≤45 bpm for 5 seconds) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia
Measured: 255 minutes
Ventricular premature beats
Difference in ventricular premature beats during hyperglycaemia compared to euglycaemia both preceded by insulin-induced hypoglycaemia
Measured: 255 minutes
Glucagon response
Differences in glucagon response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
Measured: 255 minutes
Catecholamine response
Differences in catecholamine response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
Measured: 255 minutes
Growth hormone response
Differences in growth hormone response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
Measured: 255 minutes
Cortisol response
Differences in cortisol responses during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
Measured: 255 minutes
Haemodynamic regulation.
Differences in haemodynamic regulation (measured by echocardiography) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia
Measured: 255 minutes
Inflammatory response
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
Measured: 255 minutes
Oxidative stress markers (8-iso-PGF2α)
Differences in markers of oxidative stress (8-iso prostaglandin F2α (8-iso-PGF2α)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia
Measured: 255 minutes
Oxidative stress markers (8-oxoGuo)
Differences in markers of oxidative stress (8-oxo-7,8-dihydroguanosine (8-oxoGuo)) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia
Measured: 255 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2019
- Study start1 Dec 2018
- Primary completion1 Dec 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 type1Studies 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
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, Hillerod Hospital, Denmark
- Responsible party
- Sponsor
- Investigators
- Tina Vilsbøll, MD, DMSc, Study director, Steno diabetic centre (SDCC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03956173
- Sponsor's protocol ID
- H-18034040
- Acronym
- Hypo-Heart-1
- Status last verified
- Jul 2022
- First submitted
- 12 Oct 2018
- Last updated
- 3 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03956173
- Acronym / sponsor ID
- Hypo-Heart-1 / H-18034040
- Conditions
- Diabetes type1, Hypoglycemia, Arrhythmias, Cardiac
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- University Hospital, Gentofte, Copenhagen, Hillerod Hospital, Denmark
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 20 May 2019 (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.
The investigators hypothesise that following episodes of hypoglycemia, rebound hyperglycemia may result in a prolonged period of increased QTc and, thereby, increased susceptibility to serious cardiac arrhythmias in patients with type - 1 diabetes.
Detailed description
In this study, changes in cardiac rhythm, haemodynamic regulation, and hormonal response will be evaluated during insulin-induced hypoglycemia followed by hyperglycemia and euglycemia, 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 hyperglycemic or the hypo- and euglycemic 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 hyperinsulinemic euglycemic 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 euglycemic 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 hyperinsulinemic hypoglycemic clamp. From 135 min to 195 min, plasma glucose levels will be increased to either hyperglycemic level or euglycemic level and will be kept constant for 105 minutes. Echocardiography is performed at baseline, at hypoglycemic level and at hyper-or normoglycemic 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.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clamp group | – | Other: Hypoglycemic combined with either normo or hyperglycemic clamp.24 patients with type 1 diabetes. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 24 patients with type 1 diabetes with insulin treatment for ≥ 3 years.
Key inclusion criteria (4 listed)
- Informed and written consent
- Type 1 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
- Age 18-70 years
- Insulin treatment for ≥3 years
Key exclusion criteria (6 listed)
- 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)
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 |
|---|---|---|
| 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 hyperglyemic 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. | Other | Clamp group |
Primary outcome
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
12 secondary outcomes
QTd dispersion.
Time frame: 255 minutes
Atrial ectopic beats.
Time frame: 255 minutes
Bradycardia
Time frame: 255 minutes
Ventricular premature beats
Time frame: 255 minutes
Glucagon response
Time frame: 255 minutes
Catecholamine response
Time frame: 255 minutes
Growth hormone response
Time frame: 255 minutes
Cortisol response
Time frame: 255 minutes
Haemodynamic regulation.
Time frame: 255 minutes
Inflammatory response
Time frame: 255 minutes
Oxidative stress markers (8-iso-PGF2α)
Time frame: 255 minutes
Oxidative stress markers (8-oxoGuo)
Time frame: 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 3 Dec 2024.
- Individual participant dataSharing planned: Undecided
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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 study director
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?
An observational study of Diabetes type1 and Hypoglycemia, 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 6 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 3 Dec 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 prolongation. (time frame: 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 3 Dec 2024.