Recurrent Hypoglycaemia in Type 1 Diabetes (HypoNeuro)

Recurrent Hypoglycaemia in Type 1 Diabetes: Effects on Cognitive Function, Cerebral Electrical Activity, and Skin Temperature

Patients with type 1 diabetes are at risk of very low blood sugar levels (hypoglycaemia) as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia. During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines.

The purpose of the study is to investigate the activity in the brain, the cognitive function, and the skin temperature when patients are exposed to repeated hypoglycaemia. The results will show whether the response to hypoglycaemia will change after repeated episodes.

It is our hope that results can contribute to improved understanding of hypoglycaemic EEG changes.

Study Overview

• Status: Completed
• Conditions: Hypoglycaemia
• Intervention / Treatment: Procedure: Insulin clamp

Detailed Description

Background:

Patients with type 1 diabetes are at risk of severe hypoglycaemia as a severe side effect to insulin therapy, in particular subjects who have lost warning of hypoglycaemia (hypoglycaemia unawareness). The episodes are associated with impaired quality of life and can lead to permanent brain damage and death.

During hypoglycaemia a low frequent activity can be seen with electroencephalography (EEG) as cognitive function declines. Repeated hypoglycaemic episodes result in down regulation of counter regulatory and symptomatic responses. It is not known whether a similar phenomenon is present for cerebral dysfunction as judged by EEG changes and cognitive function.

The purpose is to investigate the activity in the brain, the cognitive function, and the skin temperature when patients are exposed to repeated hypoglycaemia. The results will show whether the response to hypoglycaemia will change after repeated episodes.

The methods:

The investigators will recruit two groups of patients: Patients with hypoglycemia awareness and patients with hypoglycaemic unawareness.

The patients are exposed to hypoglycaemia on two concomitant days while the investigators record EEG and perform cognitive tests. Skin temperature is assessed by the use of thermography. If the patient has hypoglycaemic unawareness a 4 week period follows where the glycaemic control is loosened to avoid hypoglycaemia episodes and the patients is then exposed to hypoglycaemia again.

The prospect:

It is the investigators hope that results can contribute to improved understanding of hypoglycaemic EEG changes and skin temperature changes. This could be of potential benefit for patients with hypoglycaemic unawareness.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hillerød, Denmark, 3400
    • Hillerod Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 diabetes
• Age > 18 years
• - Have had diabetes for more than 5 years
• Negative pregnancy test
• Caucasian
• Signed written informed consent

Exclusion Criteria:

• Pregnant or breastfeeding
• Epilepsy
• Self-perceived impaired hearing
• Use of antiepileptic medicine
• Use of neuroleptics within the last 6 months
• Use of benzodiazepines within the last month
• Use of betablockers
• Previous stroke or other disease in the brain
• Cardiovascular disease
• Alcohol-, drug- or medicine abuse
• Previous allergic reaction to heparin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients with hypoglycemia awareness; Patients who have symptoms when the blood sugar level is low	Procedure: Insulin clamp; Patients will be exposed to low bloodsugar; Other Names: Insulin; clamp
Experimental: patients with hypoglycaemic unawareness.; Patients who do not feel any symptoms when the blood sugar levels are low	Procedure: Insulin clamp; Patients will be exposed to low bloodsugar; Other Names: Insulin; clamp

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG	EEG will be analysed in order to see whether there are any differences between aware and unaware patients during hypoglycaemia. It is our hope that the result can help develop an alarm before the patient experiences severe hypoglycaemia.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTc interval	The investigators want to investigate whether the QTc complex gets wider during hypoglycaemia. This is in order to see whether long QTc could be the explanation behind sudden dearth in diabetes patients.	2 years
Skin temperature	Skin temperature will be measured by thermography. The investigators want to see whether the skin can be used as a biomarker for hypoglycaemia.	2 years
Auditory evoked potentials	The investigators what to see whether there is any difference in auditory evoked potentials (AEP) between aware and unaware diabetic patients. The subject will hear a common and a rare sound in a 4:1 ratio while the EEG is recorded. Afterwards the data is analyzed and the AEPs are addressed.	2 years
Cognitive function	The investigators want to address whether there are any differences in the cognitive function between aware and unaware patients. The cognitive function will be addressed by the use of cognitive function tests (CalCAP) and Stroops tests as well.	2 years

Collaborators and Investigators

• Sponsor: Hillerod Hospital, Denmark
• Collaborators: Rigshospitalet, Denmark; University of Southern Denmark; UNEEG Medical A/S
• Investigators: Principal Investigator: Anne-Sophie Sejling, MD, Hillerod Hospital

Publications and helpful links

General Publications

• Rubega M, Sparacino G, Sejling AS, Juhl CB, Cobelli C. Hypoglycemia-Induced Decrease of EEG Coherence in Patients with Type 1 Diabetes. Diabetes Technol Ther. 2016 Mar;18(3):178-84. doi: 10.1089/dia.2015.0347. Epub 2016 Jan 8.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 30, 2011
• First Submitted That Met QC Criteria: April 15, 2011
• First Posted (Estimate): April 18, 2011

Study Record Updates

• Last Update Posted (Estimate): October 16, 2014
• Last Update Submitted That Met QC Criteria: October 15, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Diabetes; EEG; Hypoglycaemia; Thermography; QTc interval; Hypoglycaemia-associated autonomic failure; Hypoglycemic alarm device; Hormone response
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: H-1-2011-024