NCT05500352

Brief Summary

Patients with diabetes have an increased risk of sudden cardiac death compared to the general population. Severe hypoglycemia is associated with an increased risk of cardiovascular (CV) disease (CVD) and events, including cardiac arrhythmias and sudden cardiac death; likewise, increased glycemic variability is associated with macrovascular complications and increased mortality. The physiological mechanisms linking hypoglycemia and glycemic variability to CVD and CV events remain unclear. Myocardial work and mechanical dyssynchrony will be measured by speckle tracking echocardiography during euglycemia, hypoglycemia and hyperglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes. Echocardiographic images from three experimental clamp studies - Hypo-Heart 1 (sub-study 1), Hypo-Heart 2 (sub-study 2) and Rapid-Heart - will be included in this study.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
86

participants targeted

Target at P25-P50 for not_applicable diabetes

Timeline
Completed

Started Jul 2022

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2022

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

July 6, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

August 15, 2022

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2023

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2023

Completed
Last Updated

August 17, 2022

Status Verified

August 1, 2022

Enrollment Period

10 months

First QC Date

July 6, 2022

Last Update Submit

August 15, 2022

Conditions

DiabetesHypoglycemiaHyperglycemiaCardiovascular DiseasesSudden Cardiac Death

Outcome Measures

Primary Outcomes (1)

  • Change in the global work during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively.

    Absolute change in the global work index measured by pressure-strain loop analysis during insulin-induced hypoglycemia compared to euglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively (Hypo-Heart 1 and Hypo-Heart 2). Study outcomes will be analyzed separately for each included study.

    255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2)

Secondary Outcomes (5)

  • Primary secondary outcome: Change in mechanical dyssynchrony during hypoglycemia in individuals with type 1 diabetes, type 2 diabetes, and without diabetes, respectively.

    255 minutes (Hypo-Heart 1) and 190 minutes (Hypo-Heart 2)

  • Change in the global work during recovery in individuals with type 1 diabetes.

    255 minutes

  • Change in mechanical dyssynchrony during recovery in individuals with type 1 diabetes.

    255 minutes

  • Change in the global work during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively.

    255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2)

  • Change in mechanical dyssynchrony during hyperglycemia in individuals with type 1 diabetes, type 2 diabetes and without diabetes, respectively.

    255 minutes (Rapid Heart) and 190 minutes (Hypo-Heart 2)

Study Arms (9)

Cardiovascular effects of slowly declining plasma glucose in type 1 diabetes

EXPERIMENTAL
Other: Hyperglycemia with slow decline in plasma glucose in type 1 diabetes

Cardiovascular effects of rapidly declining plasma glucose in type 1 diabetes

EXPERIMENTAL
Other: Hyperglycemia with rapid decline in plasma glucose in type 1 diabetes

Cardiovascular effects of rebound hyperglycemia in type 1 diabetes

EXPERIMENTAL
Other: Rebound hyperglycemia in type 1 diabetes

Cardiovascular effects of rebound euglycemia in type 1 diabetes

EXPERIMENTAL
Other: Rebound euglycemia in type 1 diabetes

Cardiovascular effects of hypoglycemia in type 1 diabetes

EXPERIMENTAL
Other: Hypoglycemia in type 1 diabetes

Cardiovascular effects of hypoglycemia in type 2 diabetes

EXPERIMENTAL
Other: Hypoglycemia in type 2 diabetes

Cardiovascular effects of hypoglycemia in healthy controls

EXPERIMENTAL
Other: Hypoglycemia in healthy controls

Cardiovascular effects of hyperglycemia in type 2 diabetes

EXPERIMENTAL
Other: Hyperglycemia in type 2 diabetes

Cardiovascular effects of hyperglycemia in healthy controls

EXPERIMENTAL
Other: Hyperglycemia in healthy controls

Interventions

Hyperglycemia with slow decline in plasma glucose in type 1 diabetesOTHER

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).

Cardiovascular effects of slowly declining plasma glucose in type 1 diabetes
Hyperglycemia with rapid decline in plasma glucose in type 1 diabetesOTHER

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).

Cardiovascular effects of rapidly declining plasma glucose in type 1 diabetes
Rebound hyperglycemia in type 1 diabetesOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in hyperglycemia (20.0 mmol/L)

Also known as: Experimental clamp
Cardiovascular effects of rebound hyperglycemia in type 1 diabetes
Rebound euglycemia in type 1 diabetesOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in euglycemia (PG: 5-8 mmol/L).

Also known as: Experimental clamp
Cardiovascular effects of rebound euglycemia in type 1 diabetes
Hypoglycemia in type 1 diabetesOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (5-8 mmol/L), 2) hyperinsulinemic hypoglycemic phase (PG: 2.5 mmol/L), 3) recovery phase in hyperglycemia (20.0 mmol/L) or euglycemia (PG: 5-8 mmol/L)

Also known as: Experimental clamp
Cardiovascular effects of hypoglycemia in type 1 diabetes
Hypoglycemia in type 2 diabetesOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Also known as: Experimental clamp
Cardiovascular effects of hypoglycemia in type 2 diabetes
Hypoglycemia in healthy controlsOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Also known as: Experimental clamp
Cardiovascular effects of hypoglycemia in healthy controls
Hyperglycemia in type 2 diabetesOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Also known as: Experimental clamp
Cardiovascular effects of hyperglycemia in type 2 diabetes
Hyperglycemia in healthy controlsOTHER

Includes three steady state phases in plasma glucose, 1) euglycemic phase (fasting PG), 2) hyperglycemic phase (fasting PG + 10 mmol/L), 3) hyperinsulinemic hypoglycemic phase (PG \< 3.0 mmol/L).

Also known as: Experimental clamp
Cardiovascular effects of hyperglycemia in healthy controls

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Arrhythmia diagnosed prior to the screening visit
  • 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)
  • Hypo-Heart 2:
  • Informed and written consent
  • Type 2 diabetes diagnosed according to the criteria of the World Health Organization (WHO)
  • Treatment with insulin
  • Glycated haemoglobin A1c (HbA1c) ≤58 mmol/mol
  • HbA1c ≤42 mmol/mol
  • Fasting plasma glucose ≤6.1 mmol/l
  • Severe heart failure (left ventricular ejection fraction \<25%)
  • Structural heart disease (Wolf-Parkinson-White syndrome, congenital heart disease, severe valve disease)
  • Insulin naïve patients with type 2 diabetes
  • +31 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Steno Diabetes Center Copenhagen

Herlev, 2920, Denmark

Location

MeSH Terms

Conditions

Diabetes MellitusHypoglycemiaHyperglycemiaCardiovascular DiseasesDeath, Sudden, Cardiac

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHeart ArrestHeart DiseasesDeath, SuddenDeathPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Tina Vilsbøll

    Steno Diabetes Center Copenhagen, Denmark

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: The present echocardiographic study includes participants from three experimental clamp studies; the Hypo-Heart 1 (Study 1), Hypo-Heart 2 (Study 2) and Rapid-Heart (Study 3).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2022

First Posted

August 15, 2022

Study Start

July 1, 2022

Primary Completion

May 1, 2023

Study Completion

December 1, 2023

Last Updated

August 17, 2022

Record last verified: 2022-08

Locations

DK(1)