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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Louise Faerch, Hillerod Hospital, Denmark
ClinicalTrials.gov Identifier:
NCT01116180
First received: January 25, 2010
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
Type 1 Diabetes
Hypoglycemia
Drug: Angiotensin II receptor antagonists (Candesartan)
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Hillerod Hospital, Denmark:

Primary Outcome Measures:
  • Cognitive function and brain cortical activity assessed by EEG [ Time Frame: 2 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire [ Time Frame: 2 month ] [ Designated as safety issue: No ]
  • Hormonal counter-regulatory response and substrates [ Time Frame: 2 month ] [ Designated as safety issue: No ]
  • Blood pressure and pulse [ Time Frame: 2 month ] [ Designated as safety issue: No ]
  • Cardiac conduction evaluated by a three channel digital Holter Monitor. [ Time Frame: 2 month ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: April 2010
Study Completion Date: February 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Candesartan Drug: Angiotensin II receptor antagonists (Candesartan)
Seven days of treatment with Candesartan 32 mg, capsules.
Other Names:
  • Blopress
  • Atacand
  • Amias
  • Ratacand
Placebo Comparator: Placebo Drug: Placebo
Placebo Capsule matching the active comparator. Given for 7 days once daily.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01116180

Locations
Denmark
Department of Cardiology and Endocrinology, Hillerød Hospital
Hillerød, Denmark, 3400
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Louise Faerch, MD, ph.d.student, Hillerod Hospital, Denmark
ClinicalTrials.gov Identifier: NCT01116180     History of Changes
Other Study ID Numbers: HypoRas
Study First Received: January 25, 2010
Last Updated: February 4, 2013
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Hillerod Hospital, Denmark:
Type 1 diabetes
Hypoglycaemia
genetic susceptibility
Renin angiotensin system activity

Additional relevant MeSH terms:
Hypoglycemia
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Angiotensin II
Candesartan
Candesartan cilexetil
Angiotensin Receptor Antagonists
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014