Cognitive Function and Electrocardiogram (ECG) During Hypoglycemia and Blockade of the Renin-angiotensin System
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.
|Type 1 Diabetes Hypoglycemia||Drug: Angiotensin II receptor antagonists (Candesartan) Drug: Placebo|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Prevention
|Official Title:||Influence of Blockade of the Renin-angiotensin System for Preservation of Cognitive Function, Hormonal Counter-regulatory Response, Symptomatology and Cardiac Repolarisation During Hypoglycaemia in Patients With Type 1 Diabetes|
- Cognitive function and brain cortical activity assessed by EEG [ Time Frame: 2 month ]
- Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire [ Time Frame: 2 month ]
- Hormonal counter-regulatory response and substrates [ Time Frame: 2 month ]
- Blood pressure and pulse [ Time Frame: 2 month ]
- Cardiac conduction evaluated by a three channel digital Holter Monitor. [ Time Frame: 2 month ]
|Study Start Date:||April 2010|
|Study Completion Date:||February 2013|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
|Active Comparator: Candesartan||
Drug: Angiotensin II receptor antagonists (Candesartan)
Seven days of treatment with Candesartan 32 mg, capsules.
|Placebo Comparator: Placebo||
Placebo Capsule matching the active comparator. Given for 7 days once daily.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01116180
|Department of Cardiology and Endocrinology, Hillerød Hospital|
|Hillerød, Denmark, 3400|
|Study Director:||Ulrik Pedersen-Bjergaard, MD, MDSc.||Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød|
|Principal Investigator:||Louise Færch, MD||Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød|
|Study Director:||Birger Thorsteinsson, Prof DMSc MD||Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød. University of Copenhagen|