Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00174902
Status:
UNKNOWN
Last Update Posted:
2006-10-25
First Post:
2005-09-09
Brief Title:
The Effect of Beta-Blockers and Aspirin on Hemostasis and Endothelial Function After Acute Mental Stress
Sponsor:
Swiss Federal Institute of Technology
Organization:
Swiss Federal Institute of Technology
Study Overview
Official Title:
The Effect of Beta-Blockers Aspirin and Natural Habituation on Procoagulant Activity Expression of Cellular Adhesion Molecules and Endothelial Activation in Response to Acute Mental Stress a Randomized Controlled Trial
Status:
UNKNOWN
Status Verified Date:
2003-10
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized double-blinded controlled trial uses a factorial design to investigate whether application of beta-blockers inderal 80 mg or aspirin 100 mg or a combination thereof has an effect on the activation of the hemostatic system the platelets and the endothelium in response to acute mental stress Specifically we test the hypothesis that inderal attenuates the activation of the hemostatic system as compared to placebo The second hypothesis is that aspirin attenuates the activation of platelets as compared to placebo Subjects will be randomly allocated to either of the four following study arms placebo - inderal - aspirin - inderal plus aspirin Subjects will receive the study medication for five days prior to the mental stress The acute mental stress consists of a public speaking session of 10 min duration immediately followed by a mental arithmetic test of 5 min duration Blood will be collected prior to the stress immediately thereafter at 45 min at at 1 hour and 45 min
Detailed Description:
Background Population based studies have established hemostatic abnormalities as independent risk factors for atherosclerosis and related adverse outcomes These abnormalities are characterized as prothrombotic by elevated plasma levels of eg fibrinogen or D-dimer Prothrombotic states appear to aggravate the impact of other risk factors eg hypertension Other epidemiologic studies have shown a sizable association between chronic mental stress e g marital discord in women or acute mental stress anger and coronary heart disease A large case-crossover study attributed a 23-fold increased relative risk of acute myocardial infarction during the 2 hours following outbursts of anger This risk was modified by aspirin risk ratio of 29 in non-users risk-ratio of 14 with prior to aspirin intake We have recently shown that acute mental stress is followed by profound rises of D-dimer and induction of a prothrombotic state In real life individuals are frequently and repetitively exposed to similar stressors eg work or marital discord Those who fail to habituate and to mitigate their adrenergic responses and hemostatic changes may be at increased risk of rapid progression of atherosclerosis These individuals might particularly benefit from preventive medication with beta-blockers or aspirin
Objectives To elucidate whether administration of non-specific beta-blockers aspirin or both may abrogate the prothrombotic shift in the hemostatic balance in response to acute mental stress
To elucidate the pathway leading from central nervous system arousal after acute mental stress to increases in plasma D-dimer levels by investigating intermediate steps in the process including activation of mononuclear and endothelial cells of platelets and of hemostatic factors
To show that some individuals do not habituate when repetitively being exposed to the same stressor orand that habituation blunts the stress response as do beta-blocking medication aspirin or both
Subjects 80 healthy male and nonpregnant female non-smokers aged 40 - 55 years
Methods Randomized double-blind two-by-two factorial design A public speaking stress will be applied in two different experiments 1 The first experiment consists of a habituation study wherein 20 subjects will be stressed three times with intervals of 1 week apart 2 The second experiment consists of a medication study wherein 60 individuals other than those taking part in the habituation study will be randomly assigned to one of the following four arms 1 placeboplacebo 2 placebobeta-blocker 3 placeboaspirin 4 beta-blockeraspirin Beta-blocker medication consists of 80 mgday of propranolol Inderal LA 80 aspirin will be given in a dose of 100 mgday Blood will be collected before immediately after and at 45 min and at 1 hour and 45 min after the stress task in both experiments In both experiments subjects will be fully debriefed after the first stressor The primary dependent variable is the change score of plasma levels of D-dimer after the stressor Data will be analyzed by two-way ANOVA with the experimental condition being the first factor and with the experiment repetition being the second factor Intermediate variables measured for elucidating the biological pathway leading to changes in D-dimer are a arousal of neuro-endocrine circuits plasma levels of epinephrine and nor-epinephrine salivary cortisol levels b activation alteration of circulating mononuclear cells quantitative determination of subpopulations by flow-cytometry expression of L-selectin CD62L lymphocyte function associated antigen 1 LFA-1 CD154 expressed on activated T-lymphocytes and tissue-factor on monocytes c activation of endothelial cells plasma levels of soluble intercellular adhesion molecule 1 sICAM-1 soluble vascular cellular adhesion molecule 1 sVCAM-1 endothelin-1 and von Willebrand factor vWF d balance between prothrombotic and fibrinolytic activity plasma levels of D-dimer fibrinogen thrombinantithrombin III complexes tissue plasminogen activator and plasminogen activator inhibitor-1
Objectives To elucidate whether administration of non-specific beta-blockers aspirin or both may abrogate the prothrombotic shift in the hemostatic balance in response to acute mental stress
To elucidate the pathway leading from central nervous system arousal after acute mental stress to increases in plasma D-dimer levels by investigating intermediate steps in the process including activation of mononuclear and endothelial cells of platelets and of hemostatic factors
To show that some individuals do not habituate when repetitively being exposed to the same stressor orand that habituation blunts the stress response as do beta-blocking medication aspirin or both
Subjects 80 healthy male and nonpregnant female non-smokers aged 40 - 55 years
Methods Randomized double-blind two-by-two factorial design A public speaking stress will be applied in two different experiments 1 The first experiment consists of a habituation study wherein 20 subjects will be stressed three times with intervals of 1 week apart 2 The second experiment consists of a medication study wherein 60 individuals other than those taking part in the habituation study will be randomly assigned to one of the following four arms 1 placeboplacebo 2 placebobeta-blocker 3 placeboaspirin 4 beta-blockeraspirin Beta-blocker medication consists of 80 mgday of propranolol Inderal LA 80 aspirin will be given in a dose of 100 mgday Blood will be collected before immediately after and at 45 min and at 1 hour and 45 min after the stress task in both experiments In both experiments subjects will be fully debriefed after the first stressor The primary dependent variable is the change score of plasma levels of D-dimer after the stressor Data will be analyzed by two-way ANOVA with the experimental condition being the first factor and with the experiment repetition being the second factor Intermediate variables measured for elucidating the biological pathway leading to changes in D-dimer are a arousal of neuro-endocrine circuits plasma levels of epinephrine and nor-epinephrine salivary cortisol levels b activation alteration of circulating mononuclear cells quantitative determination of subpopulations by flow-cytometry expression of L-selectin CD62L lymphocyte function associated antigen 1 LFA-1 CD154 expressed on activated T-lymphocytes and tissue-factor on monocytes c activation of endothelial cells plasma levels of soluble intercellular adhesion molecule 1 sICAM-1 soluble vascular cellular adhesion molecule 1 sVCAM-1 endothelin-1 and von Willebrand factor vWF d balance between prothrombotic and fibrinolytic activity plasma levels of D-dimer fibrinogen thrombinantithrombin III complexes tissue plasminogen activator and plasminogen activator inhibitor-1
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None