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

• Sponsor: University of Aarhus (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT03034226
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 31.2
• Patients Per Site Per Month: 0.6

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Hypoglycemia; Diabetes Mellitus, Type 1	Other: Glucose clamp technique	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention 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).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)
• Primary Purpose: Prevention
• Official Title: A Comparison Between Counter Regulatory Responses in Type 1 Diabetic Patients Versus Healthy Control Subjects With and Without Antecedent Hypoglycemia
• Actual Study Start Date: Feb 23, 2017
• Actual Primary Completion Date: Feb 1, 2018
• Anticipated Study Completion Date: Oct 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Single episode of hypoglycemia Day 1: Hyperinsulinemic hypoglycemic clamp 30 min Day 2: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours	Other: Glucose clamp technique; Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose
Active Comparator: Two episodes of hypoglycemia Day 3: No intervention (normal blood glucose) Day 4: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours	Other: Glucose clamp technique; Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose

Outcome Measures

Primary Outcome Measures

1. Insulin sensitivity [Day 2 and day 4 (T=60 minutes - T=240 minutes)]

   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

1. Hormonal counter regulatory response to hypoglycemia [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]

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

2. Symptoms during hypoglycemia [Day 2 and day 4 (T=0 minutes - T=420 minutes)]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Clinical Medicine	Aarhus		Denmark	8000

Sponsors and Collaborators

• University of Aarhus

Investigators

• Principal Investigator: Mads Bisgaard Bengtsen, MD, phd student, Department of Endocrinology and Internal Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT03034226
• Other Study ID Numbers: Project 1-10-72-304-16
• First Posted: Jan 27, 2017
• Last Update Posted: Mar 21, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Aarhus: Hypoglycemia-Associated Autonomic Failure (HAAF)
• Additional relevant MeSH terms: Hypoglycemia; Diabetes Mellitus, Type 1

Study Results

No Results Posted as of Mar 21, 2018