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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Type 1 Diabetes
• Intervention / Treatment: Drug: Angiotensin II receptor antagonists (Candesartan); Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hillerød, Denmark, 3400
    • Department of Cardiology and Endocrinology, Hillerød Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo Capsule matching the active comparator. Given for 7 days once daily.
ACTIVE_COMPARATOR: Candesartan	Drug: Angiotensin II receptor antagonists (Candesartan); Seven days of treatment with Candesartan 32 mg, capsules.; Other Names: Blopress; Amias; Ratacand; Atacand

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cognitive function and brain cortical activity assessed by EEG	2 month

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Louise Faerch
• Investigators: 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

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: January 25, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (ESTIMATE): May 4, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): February 5, 2013
• Last Update Submitted That Met QC Criteria: February 4, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Type 1 diabetes; genetic susceptibility; Hypoglycaemia; Renin angiotensin system activity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Vasoconstrictor Agents; Candesartan; Angiotensin II; Giapreza; Angiotensinogen; Angiotensin Receptor Antagonists
• Other Study ID Numbers: HypoRas