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Hypothesis: Treating patients with type 1 diabetes with a certain antihypertensive drug preserve cerebral function during hypoglycaemia.
Background: Studies have found that certain genetic variations leaves a subject with type 1 diabetes more prone to hypoglycaemia. It it thought to be a decline in cognition during hypoglycaemia that leaves them at risk of severe hypoglycaemia. The idea is tha when you suppress the genetic phenotype with a well known antihypertensive drug an improvement in cognition will occur and this will remove the patients tendency to severe hypoglycaemia.
Methods: The investigators want to explore whether the cerebral function is improved during hypoglycaemia in subjects with type 1 diabetes and the above mentioned genetic variation when treated with the antihypertensive drug Candesartan.
We will include 25 type 1 diabetic patients from our outpatient clinic. They are already genotyped from another trial.
Each patient goes through two cycles with hyperinsulinemic glucose clamp induced hypoglycemia. The study is double blinded, randomised and placebocontrolled so the patients receive both Candesartan and placebo but in different cycles.
In each cycle patients will receive either Candesartan or placebo for 7 days. After 8 days patients undergo a hypoglycaemic clamp during which primary and secondary endpoints will be measured.
In the hyperinsulinemic hypoglycaemic clamp the patients will undergo an adjustment period towards euglycaemia. A period of approximately 1 hour of euglycemia, an hour of hypoglycemia and a period of recovery towards euglycemia. In each of these glycemic states primary and secondary outcomes will be measured.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Candesartan | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Angiotensin II receptor antagonists (Candesartan) | Drug | Seven days of treatment with Candesartan 32 mg, capsules. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive function and brain cortical activity assessed by EEG | 2 month |
| Measure | Description | Time Frame |
|---|---|---|
| Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire | 2 month | |
| Hormonal counter-regulatory response and substrates | 2 month | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ulrik Pedersen-Bjergaard, MD, MDSc. | Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød | Study Director |
| Louise Færch, MD | Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød | Principal Investigator |
| Birger Thorsteinsson, Prof DMSc MD | Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød. University of Copenhagen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiology and Endocrinology, Hillerød Hospital | Hillerød | 3400 | Denmark |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D007003 | Hypoglycemia |
| D020022 | Genetic Predisposition to Disease |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D057911 | Angiotensin Receptor Antagonists |
| C081643 | candesartan |
| C077793 | candesartan cilexetil |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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| Placebo | Drug | Placebo Capsule matching the active comparator. Given for 7 days once daily. |
|
| Blood pressure and pulse |
| 2 month |
| Cardiac conduction evaluated by a three channel digital Holter Monitor. | 2 month |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D004198 | Disease Susceptibility |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |