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Comparison Between Hypoglycemic Counter Regulatory Responses in Type 1 Diabetics vs Control Subjects

Primary Purpose

Hypoglycemia, Diabetes Mellitus, Type 1

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Glucose clamp technique

About this trial

This is an interventional prevention trial for Hypoglycemia focused on measuring Hypoglycemia-Associated Autonomic Failure (HAAF)

Eligibility Criteria

20 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

Type 1 diabetics

Inclusion Criteria:

More than 5 years of disease duration
HbA1c 42-86 mmol/L
No known HAAF
BMI 22-28
Written consent

Exclusion Criteria:

Other disease than diabetes f.x epilepsy, ischemic heart disease or heart rhythm disturbance
Medication f.x beta-blockade, steroids, psychotropics
Smoking
Drug abuse

Control subjects

Inclusion Criteria:

BMI 22-28
Written consent

Exclusion Criteria:

Diseases f.x diabetes, epilepsy, ischemic heart disease or heart rhythm disturbance
Medication f.x beta-blockade, steroids, psychotropics
Smoking
Drug abuse

Sites / Locations

Department of Clinical Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Single episode of hypoglycemia

Two episodes of hypoglycemia

Arm Description

Day 1: Hyperinsulinemic hypoglycemic clamp 30 min Day 2: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours

Day 3: No intervention (normal blood glucose) Day 4: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours

Outcomes

Primary Outcome Measures

Insulin sensitivity

Insulin sensitivity before, during hypoglycemia and after recovery from hypoglycemia on day 2 (one episode of hypoglycemia) compared with day 4 (two consecutive episodes of hypoglycemia). Insulin sensitivity is measured as M-value derived from the Glucose Infusion Rate (GIR) during a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp

Secondary Outcome Measures

Hormonal counter regulatory response to hypoglycemia

Hormonal counter regulatory response (epinephrine, norepinephrine, glucagon, cortisol, ghrelin etc.) measured regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp

Symptoms during hypoglycemia

Using the Edinburgh Hypoglycemia Scale (symptom scale) we will interview the subjects regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp

Full Information

NCT ID

NCT03034226

First Posted

January 17, 2017

Last Updated

October 4, 2022

Sponsor

University of Aarhus

1. Study Identification

Unique Protocol Identification Number

NCT03034226

Brief Title

Comparison Between Hypoglycemic Counter Regulatory Responses in Type 1 Diabetics vs Control Subjects

Official Title

A Comparison Between Counter Regulatory Responses in Type 1 Diabetic Patients Versus Healthy Control Subjects With and Without Antecedent Hypoglycemia

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

February 23, 2017 (Actual)

Primary Completion Date

February 1, 2018 (Actual)

Study Completion Date

January 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Aarhus

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study compares the hypoglycemic counter regulatory response in type 1 diabetics and in healthy control subjects with and without antecedent hypoglycemia

Detailed Description

Iatrogenic hypoglycemia is one of the main limiting factors for optimal glycemic management of diabetes. It causes recurrent morbidity in most people with type 1 diabetes and in many patients with type 2 diabetes and can be fatal. Episodes of hypoglycemia impair physiologically protective mechanism in subsequent episodes of hypoglycemia. This phenomenon is known as hypoglycemia-associated autonomic failure (HAAF), the clinical syndromes of defective glucose counter regulation and hypoglycemia unawareness.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypoglycemia, Diabetes Mellitus, Type 1

Keywords

Hypoglycemia-Associated Autonomic Failure (HAAF)

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

9 diabetic subjects and 9 healthy control subjects will be randomized to undergo either first day 1 + day 2 (two consecutive episode of hypoglycemia) or first day 3 + day 4 (one episode of hypoglycemia).

Masking

None (Open Label)

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single episode of hypoglycemia

Arm Type

Active Comparator

Arm Description

Day 1: Hyperinsulinemic hypoglycemic clamp 30 min Day 2: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours

Arm Title

Two episodes of hypoglycemia

Arm Type

Active Comparator

Arm Description

Day 3: No intervention (normal blood glucose) Day 4: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours

Intervention Type

Other

Intervention Name(s)

Glucose clamp technique

Intervention Description

Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose

Primary Outcome Measure Information:

Title

Insulin sensitivity

Description

Time Frame

Day 2 and day 4 (T=60 minutes - T=240 minutes)

Secondary Outcome Measure Information:

Title

Hormonal counter regulatory response to hypoglycemia

Description

Time Frame

Day 2 and day 4 (T=0 minutes, T=30, T=40, T=50, T=120, T=130, T=140, T160, T=170, T=180, T=210, T=220, T=230, T=390, T=400 and T=410

Title

Symptoms during hypoglycemia

Description

Using the Edinburgh Hypoglycemia Scale (symptom scale) we will interview the subjects regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp

Time Frame

Day 2 and day 4 (T=0 minutes - T=420 minutes)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Type 1 diabetics Inclusion Criteria: More than 5 years of disease duration HbA1c 42-86 mmol/L No known HAAF BMI 22-28 Written consent Exclusion Criteria: Other disease than diabetes f.x epilepsy, ischemic heart disease or heart rhythm disturbance Medication f.x beta-blockade, steroids, psychotropics Smoking Drug abuse Control subjects Inclusion Criteria: BMI 22-28 Written consent Exclusion Criteria: Diseases f.x diabetes, epilepsy, ischemic heart disease or heart rhythm disturbance Medication f.x beta-blockade, steroids, psychotropics Smoking Drug abuse

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mads Bisgaard Bengtsen, MD, phd student

Organizational Affiliation

Department of Endocrinology and Internal Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Clinical Medicine

City

Aarhus

ZIP/Postal Code

8000

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

32927476

Citation

Bengtsen MB, Stoy J, Rittig NF, Voss TS, Magnusson NE, Svart MV, Jessen N, Moller N. A Human Randomized Controlled Trial Comparing Metabolic Responses to Single and Repeated Hypoglycemia in Type 1 Diabetes. J Clin Endocrinol Metab. 2020 Dec 1;105(12):dgaa645. doi: 10.1210/clinem/dgaa645.

Results Reference

derived

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Comparison Between Hypoglycemic Counter Regulatory Responses in Type 1 Diabetics vs Control Subjects

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