Cognitive Function and Electrocardiogram (ECG) During Hypoglycemia and Blockade of the Renin-angiotensin System

Not Applicable

Completed

• Conditions: Type 1 Diabetes; Hypoglycemia
• Interventions: Drug: Placebo; Drug: Angiotensin II receptor antagonists (Candesartan)

• Registration Number: NCT01116180
• Lead Sponsor: Louise Faerch

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.

Study Timeline

• Study First Submitted: 2010-01-25
• Study Start: 2010-04
• Study First Submitted QC: 2010-05-03
• Study First Posted: 2010-05-04
• Primary Completion: 2012-08
• Status Verified: 2013-02
• Study Completion: 2013-02
• Last Update Submitted: 2013-02-04
• Last Update Posted: 2013-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Candesartan	Angiotensin II receptor antagonists (Candesartan)	-

Primary Outcome Measures

Name	Time	Method
Cognitive function and brain cortical activity assessed by EEG	2 month

Secondary Outcome Measures

Name	Time	Method
Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire	2 month
Hormonal counter-regulatory response and substrates	2 month
Blood pressure and pulse	2 month
Cardiac conduction evaluated by a three channel digital Holter Monitor.	2 month

Trial Locations

Locations (1)

Department of Cardiology and Endocrinology, Hillerød Hospital; 🇩🇰 Hillerød, Denmark