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

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01116180
• Other study ID #: HypoRas
• Status: Completed
• Phase: N/A
• First received: January 25, 2010
• Last updated: February 4, 2013
• Start date: April 2010
• Est. completion date: February 2013

Study information

• Verified date: February 2013
• Source: Hillerod Hospital, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: February 2013
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes

Intervention

Drug:
• Angiotensin II receptor antagonists (Candesartan)
Seven days of treatment with Candesartan 32 mg, capsules.
• Placebo
Placebo Capsule matching the active comparator. Given for 7 days once daily.

Locations

Country	Name	City	State
Denmark	Department of Cardiology and Endocrinology, Hillerød Hospital	Hillerød

Sponsors (1)

Lead Sponsor	Collaborator
Louise Faerch

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive function and brain cortical activity assessed by EEG		2 month	No
Secondary	Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire		2 month	No
Secondary	Hormonal counter-regulatory response and substrates		2 month	No
Secondary	Blood pressure and pulse		2 month	No
Secondary	Cardiac conduction evaluated by a three channel digital Holter Monitor.		2 month	No