The Effects of Social Support and Oxytocin Administration on Physiological Stress Reactivity in Essential Hypertension

Study Overview
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Brief Summary
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To test a psychopharmacological intervention strategy which may provide new insights into the mechanisms underlying the physiological hyperreactivity to stress observed in hypertension, we plan to test the effects of the neuropeptide oxytocin and social support on the neurobiological and psychological responsiveness to social stress. The study population for this project consists of 80 hypertensive and 80 normotensive non-smoking medication-free men. We expect exogenous oxytocin administration to enable hypertensives to effectively take advantage of the provided social support. Thereby, oxytocin may enhance the effect of social support on reducing the previously observed physiological hyperreactivity to stress in essential hypertensives.

Detailed Description
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Background Data on psychobiological stress reactivity in essential hypertension demonstrated physiological hyperreactivity to acute psychosocial stress in hypertensives as compared to normotensive controls in terms of sympathetic nervous system and hypothalamus-pituitary-adrenal axis activity, blood lipids, and coagulation activity. Moreover, we found lower perceived social support in hypertensives as compared to normotensives, with the highest physiological stress responses in hypertensives with low perceived social support.. In addition, the collaborating group of Prof. Heinrichs demonstrated that OT and social support interact to reduce neuroendocrine responses to stress in normotensive individuals. Given these findings and given the aforementioned hypothesized role for OT in physiological stress reactivity, particularly in hypertension, it seems promising to investigate the combined effects of OT and social support provision on physiological stress reactivity in essential hypertensives as compared to normotensives. Objective The proposed project will provide new information on neuroendocrine mechanisms underlying the observed physiological hyperreactivity to stress in essential hypertension. Moreover, stress reactivity of intermediate biological risk factors has not yet been investigated in experiments studying the effects of the acutely provided social support, either in healthy individuals or in hypertensives. The results of this project may provide important information for the development of effective interdisciplinary prevention and intervention strategies for essential hypertension Methods The methodological approach of social stress induction by the TSST used in our previous hypertension study will be translated to the planned project and we will repeatedly collect blood and saliva samples to measure neuroendocrine reactivity in terms of cortisol, epinephrine, and norepinephrine, as well as continuously measuring of heart rate and blood pressure. Blood pressure will be measured at each sampling timepoint as well as twice during the TSST (during the speech and during mental arithmetics). As our recent findings suggest strong associations between social support and heightened coagulation activity in healthy subjects before and after social stress, and as we found higher lipid and coagulation reactivity to psychosocial stress in hypertensives with catecholamine stress changes predicting elevated lipid stress reactivity, we plan to additionally measure biological risk factors for CHD.

Official Title
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The Effects of Social Support and Oxytocin Administration on Physiological Stress Reactivity in Essential Hypertension

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Syntocinon-Spray
* Drug: Placebo of syntocinon
* Behavioral: Social support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged between 18 and 80 years sufficient knowledge of German language in reading and understanding medication-free non-smoking systolic blood pressure ≥ 140 < 180 mmHg and/or diastolic blood pressure ≥ 90 < 110 mmHg for the hypertension group systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg for the normotensive control written informed consent Exclusion Criteria any alcohol, caffeine, and theine consumption 24 hours before the experiment regular strenuous exercise alcohol and illicit drug abuse liver and renal diseases chronic obstructive pulmonary disease allergies and atopic diathesis rheumatic diseases HIV cancer psychiatric and neurological diseases current infectious diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypertensives with oxytocin and social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Syntocinon-Spray<br>* Intranasal oxytocin (24 IU)<br>Behavioral: Social support<br>* Social support from the best friend<br>|
| Experimental: Hypertensives with oxytocin without social support<br>80 normotensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Syntocinon-Spray<br>* Intranasal oxytocin (24 IU)<br>|
| Experimental: Hypertensives without oxytocin with social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Placebo of syntocinon<br>* Intranasal administration<br>Behavioral: Social support<br>* Social support from the best friend<br>|
| Placebo Comparator: Hypertensives without oxytocin or social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Placebo of syntocinon<br>* Intranasal administration<br>|
| Experimental: Normotensives with oxytocin and social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Syntocinon-Spray<br>* Intranasal oxytocin (24 IU)<br>Behavioral: Social support<br>* Social support from the best friend<br>|
| Experimental: Normotensives with oxytocin without social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Syntocinon-Spray<br>* Intranasal oxytocin (24 IU)<br>|
| Experimental: Normotensives without oxytocin with social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Placebo of syntocinon<br>* Intranasal administration<br>Behavioral: Social support<br>* Social support from the best friend<br>|
| Placebo Comparator: Normotensives without oxytocin or social support<br>80 hypertensive non-smoking medication-free men will be randomly assigned to receive intranasal OT (24 IU) or placebo 50 min before stress, and either social support (SS) from their best friend during the preparation period of the stress protocol or no social support. | Drug: Placebo of syntocinon<br>* Intranasal administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipids from baseline |  | At 110 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipids from baseline |  | At 45, 80, 120, 130, and 170 minutes | 
| Change in catecholamines from baseline |  | At 45, 80, 110, 120, 130, 140, 155, and 170 minutes | 
| Change in cortisol from baseline |  | At 45, 80, 110, 120, 130, 140, 155, 170, 200, and 230 minutes | 
| Change in cytokine level from baseline |  | At 45, 80, 110, 120, 200, and 230 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trier social stress test, Oxytocin, Hypertension