A Trial Investigating the Effect of Acute Hypoglycaemia on Cognitive Function and Brain Activation Patterns in Subjects With Type 1 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of the trial is to compare cognitive function and associated brain activation patterns during an acute hypoglycaemic episode and during euglycaemia (normal blood glucose concentration). Additionally, the purpose is to assess cognitive function in the recovery phase after hypoglycaemia or euglycaemia, respectively, in subjects with type 1 diabetes.

Official Title
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A Trial Investigating the Effect of Acute Hypoglycaemia on Cognitive Function and Brain Activation Patterns in Subjects With Type 1 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Other: glucose clamp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right-handed subjects Type 1 diabetes mellitus for at least 12 months Treated with multiple daily insulin injections or continuous subcutaneous insulin infusion (CSII) for at least 12 months Body mass index 18.0-28.0 kg/m^2 (both inclusive) Exclusion Criteria: Subject who has donated any blood or plasma in the past month or more than 500 mL within 3 months prior to screening Current tobacco user (any smoking or use of nicotinic products within 3 months prior to screening) Visual impairment or auditory impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hypoglycaemia / euglycaemia clamp<br> | Other: glucose clamp<br>* Each subject will be randomly allocated to an experimental visit sequence consisting of a hypoglycaemic glucose clamp followed by euglycaemic glucose clamp (using i.v. infusion of human soluble insulin (Actrapid®)) or vice versa separated by at least 21 days. Each visit includes an overnight stay. For each of the two conditions (euglycaemia and hypoglycaemia) cognitive performance will be assessed by a validated cognitive test<br>|
| Other: Euglycaemia clamp / hypoglycaemia<br> | Other: glucose clamp<br>* Each subject will be randomly allocated to an experimental visit sequence consisting of a hypoglycaemic glucose clamp followed by euglycaemic glucose clamp (using i.v. infusion of human soluble insulin (Actrapid®)) or vice versa separated by at least 21 days. Each visit includes an overnight stay. For each of the two conditions (euglycaemia and hypoglycaemia) cognitive performance will be assessed by a validated cognitive test<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digit Symbol Substitution Test (DSST) score |  | Average score during hypoglycaemia and/or euglycaemia measured 70-93 minutes after induction of hypoglycaemia and/or euglycaemia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional cerebral blood flow (rCBF) score |  | Average score during hypoglycaemia and/or euglycaemia measured 70-93 minutes after induction of hypoglycaemia and/or euglycaemia | 
| Paced Auditory Serial Addition Task (PASAT) score |  | During recovery from hypoglycaemia and/or euglycaemia measured 75-90 min after euglycaemia has been restored |