Clinical trial NCT01116180: Cognitive Function and Electrocardiogram (ECG) During Hypoglycemia and Blockade of the Renin-angiotensin System
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Hypoglycemia
Keywords: Type 1 diabetes
Hypoglycaemia
genetic susceptibility
Renin angiotensin system activity
Lead sponsor: Hillerod Hospital, Denmark
Sponsor class: OTHER
First posted: 2010-05-04
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes
* Danish spoken and written
* RAS activity score\>7 - diabetes duration \> 5 years
* not pregnant and safe anticonception
* Signed informed consent.

Exclusion Criteria:

* Treatment with an ACE blocker
* An ARB og a renin blocker
* Treatment with other antihypertensive drugs
* Severe diabetic late complications
* Renal impairment
* Pregnancy and breastfeeding
* Previous reactions to study medication
* Heart insufficiency (NYHA 3-4)\\
* Known ischaemic heart disease
* Epilepsy
* Alcohol and drug abuse
* Suspicion of non-compliance,
* Plasma potassium \< 3.5 mmol/l or \>5.0 mmol/l.

Primary outcomes:
measure: Cognitive function and brain cortical activity assessed by EEG
timeFrame: 2 month
Secondary outcomes:
measure: Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire
timeFrame: 2 month
measure: Hormonal counter-regulatory response and substrates
timeFrame: 2 month
measure: Blood pressure and pulse
timeFrame: 2 month
measure: Cardiac conduction evaluated by a three channel digital Holter Monitor.
timeFrame: 2 month
Other outcomes:
Locations:
city: Hillerød
country: Denmark
facility: Department of Cardiology and Endocrinology, Hillerød Hospital
Study officials:
affiliation: Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød
name: Ulrik Pedersen-Bjergaard, MD, MDSc.
role: STUDY_DIRECTOR
affiliation: Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød
name: Louise Færch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hillerød Hospital, Department of Cardiology and Endocrinology, Dyrehavevej 29, 3400 Hillerød. University of Copenhagen
name: Birger Thorsteinsson, Prof DMSc MD
role: STUDY_DIRECTOR
References: