Ability of Metoprolol to Alter the Exercise Induced Elevation of Catecholamines

Study Overview
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Brief Summary
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Heart failure is a frequent disease in Denmark, and it is associated with very high mortality. Around 60,000 people in Denmark have heart failure, and there is about 11,000 hospitalizations every year due to this disease. From the time of diagnosis, patients survive an average of 4-5 years. A critical illness mechanism in heart failure is that these patients have high blood levels of catecholamines; epinephrine and norepinephrine, which is stress hormones from the sympathetic nervous system. Standard treatment of heart failure is with the two medical preparations betablockers and ACE-inhibitors. It is not known what effect betablocker-treatment have on blood concentration of epinephrine and norepinephrine. It is the purpose of this study, to investigate the effect of Selo-Zok ® (metoprolol) on the blood concentration of epinephrine and norepinephrine. This is done by creating a stress condition for the body, in this case with the bicycle test, while doing blood samples to determine the concentration of catecholamines. This will be done by 1-week treatment of tablet Selo-Zok ® followed by 1-week treatment of placebo (a substance with no medical effect). Blood samples will be taken to determine small changes in inheritance material (DNA) in the form of point mutations also called single nucleotide polymorphisms, since these changes can affect how we respond to metoprolol treatment.

Official Title
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A Randomised, Double Blinded, Crossover Study of the Influence of Metoprolol on Exercise Induced Elevation of Catecholamines in Healthy Subjects.

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Metoprolole (Selo-Zok ®)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kaukaser Healthy men 18 years < age < 30 years Non-smoker 18 < BMI < 25 No chronic diseases Motor-disability that disables completement of cardio-pulmonary exercise-test. Exclusion Criteria: Alcohol abuse or any other abuse Intake of any narcotic drugs (example: cannabinoids, narcotics, stimulants of central nervous system, hypnotics, hallucinogenes) Any of following medication: astmamedication heartmedication antihistamines antipsycotics NSAIDs rifampicine chinidine glucocorticoids Abnormal ECG, particularly 2. or 3. degree AV-block, sinusbradycardia, sick sinusnode-syndrome, sign of heart failure or ischemia. Allergy or intolerance of metoprolole Lactoseallergy 110 mmHg < Systolic blood pressure < 140 mmHg 60 mmHg < Diastolic blood pressure < 90 mmHg Bloodsucker > 11,1 mmol/L, or fasting, venous bloodsucker >= 7,0 (measured if: 7,8 < BS < 11,1)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Metoprolol for 10 days followed by placebo for 7 days. | Drug: Metoprolole (Selo-Zok ®)<br>* Tablets, 200 mg, once a day, 10 days<br>Drug: Placebo<br> <br> |
| Placebo Comparator: 2<br>Placebo for 7 days followed by Metoprolol for 10 days | Drug: Metoprolole (Selo-Zok ®)<br>* Tablets, 200 mg, once a day, 10 days<br>Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in stress-triggered response of catecholamines. |  | 2 weeks and 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in stress-triggered blood pressure response. |  | 2 weeks and 3 days | 
| Change in stress-triggered pulse response. |  | 2 weeks and 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SNP, catecholamines, metoprolole, healthy subjects, physiological stress