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出境医 / 临床实验 / Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes (Hypo-Heart-1)
Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes (Hypo-Heart-1)
Study Description
Brief 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.
| 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 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
| 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 |
Arms and Interventions
| 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 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.
|
Outcome Measures
Primary Outcome Measures :
- 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 :
- QTd dispersion. [ Time Frame: 255 minutes ]Difference in QT dispersion (QTd) during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
- 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
- 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
- Ventricular premature beats [ Time Frame: 255 minutes ]Difference in ventricular premature beats during hyperglycaemia compared to euglycaemia both preceded by insulin-induced hypoglycaemia
- Glucagon response [ Time Frame: 255 minutes ]Differences in glucagon response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
- Catecholamine response [ Time Frame: 255 minutes ]Differences in catecholamine response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
- Growth hormone response [ Time Frame: 255 minutes ]Differences in growth hormone response during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
- Cortisol response [ Time Frame: 255 minutes ]Differences in cortisol responses during hyperglycemia compared to euglycemia both preceded by insulin induced hypoglycemia
- Haemodynamic regulation. [ Time Frame: 255 minutes ]Differences in haemodynamic regulation (measured by echocardiography) during hyperglycemia compared to euglycemia both preceded by insulin-induced hypoglycemia
- 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
- 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
- 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
Eligibility Criteria
| 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)
- Anemia (male: hemoglobin <8.0; female: hemoglobin <7.0 mmol/l)
Contacts and Locations
Locations
| Denmark | |
| Clinical Metabolic Physiology, SDCC | |
| Copenhagen, Denmark, 2900 | |
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
University Hospital, Gentofte, Copenhagen
Hillerod Hospital, Denmark
Investigators
| Study Director: | Tina Vilsbøll, MD, DMSc | Steno diabetic centre (SDCC) |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date | October 12, 2018 | ||||
| First Posted Date | May 20, 2019 | ||||
| Last Update Posted Date | October 22, 2020 | ||||
| Actual Study Start Date | December 1, 2018 | ||||
| Estimated Primary Completion Date | December 2021 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures |
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
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| Original Primary Outcome Measures | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures |
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| Original Secondary Outcome Measures |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title | Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes | ||||
| Official Title | Hypoglycemia and Cardiac Arrhythmias in Type 1 Diabetes | ||||
| Brief 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. | ||||
| 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 Type | Observational | ||||
| Study Design | Observational Model: Case-Crossover Time Perspective: Prospective |
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| Target Follow-Up Duration | Not Provided | ||||
| Biospecimen | Not Provided | ||||
| Sampling Method | Non-Probability Sample | ||||
| Study Population | 24 patients with type 1 diabetes with insulin treatment for ≥ 3 years. | ||||
| Condition |
|
||||
| Intervention | 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 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.
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| Study Groups/Cohorts | Clamp group
24 patients with type 1 diabetes.
Intervention: Other: Hypoglycemic combined with either normo or hyperglycemic clamp.
|
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status | Active, not recruiting | ||||
| Estimated Enrollment |
24 | ||||
| Original Estimated Enrollment | Same as current | ||||
| Estimated Study Completion Date | December 2021 | ||||
| Estimated Primary Completion Date | December 2021 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender |
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| Ages | 18 Years to 80 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers | No | ||||
| Contacts | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries | Denmark | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number | NCT03956173 | ||||
| Other Study ID Numbers | H-18034040 | ||||
| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement |
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| Responsible Party | Steno Diabetes Center Copenhagen | ||||
| Study Sponsor | Steno Diabetes Center Copenhagen | ||||
| Collaborators |
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| Investigators |
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| PRS Account | Steno Diabetes Center Copenhagen | ||||
| Verification Date | October 2020 | ||||
