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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01116180
Recruitment Status : Completed
First Posted : May 4, 2010
Last Update Posted : February 5, 2013
Information provided by (Responsible Party):
Louise Faerch, Hillerod Hospital, Denmark

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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Hypoglycemia Drug: Angiotensin II receptor antagonists (Candesartan) Drug: Placebo Not Applicable

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  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, 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
Study Start Date : April 2010
Actual Primary Completion Date : August 2012
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Cognitive function and brain cortical activity assessed by EEG [ Time Frame: 2 month ]

Secondary Outcome Measures :
  1. Symptoms of hypoglycaemia assessed by Edinburgh Hypoglycaemia Symptom Score questionnaire [ Time Frame: 2 month ]
  2. Hormonal counter-regulatory response and substrates [ Time Frame: 2 month ]
  3. Blood pressure and pulse [ Time Frame: 2 month ]
  4. Cardiac conduction evaluated by a three channel digital Holter Monitor. [ Time Frame: 2 month ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01116180

Department of Cardiology and Endocrinology, Hillerød Hospital
Hillerød, Denmark, 3400
Sponsors and Collaborators
Louise Faerch
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

Responsible Party: Louise Faerch, MD, ph.d.student, Hillerod Hospital, Denmark Identifier: NCT01116180     History of Changes
Other Study ID Numbers: HypoRas
First Posted: May 4, 2010    Key Record Dates
Last Update Posted: February 5, 2013
Last Verified: February 2013

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

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Candesartan cilexetil
Angiotensin Receptor Antagonists
Angiotensin II
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors