Trial document




drksid header

  DRKS00016597

Trial Description

start of 1:1-Block title

Title

The moderating role of inflammatory and serotonergic genes on cardiovascular
stress reactivity in recently bereaved adults

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

BIR

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Purpose of the study: Research indicates that the death of a close person is not only a very stressful event, but also temporarily affects the risk of cardiovascular disease in some people.
The aim of this study is to investigate possible factors that might contribute to this increased risk of disease in order to be able to preventively treat people at risk in the future. On the one hand, this includes certain genetic characteristics that can favour an increase of inflammatory markers in blood, especially in stressful situations. On the other hand, vagus nerve activity is studied, which is associated with the regulation of heart activity, feelings and the regulation of circulating inflammatory markers. The subject of the study are the interactions between individual grief, vagus nerve activity and certain genetic characteristics.


Study procedure: The study consists of a circa 90-minute lab visit at the Clinic for Psychosomatic Medicine and Psychotherapy in Ulm. Potential study participants are women and men between 50 and 70 years who have lost a loved one (parent, sibling, spouse, child) in the last 6-24 months.
After written consent, height and weight are measured and a blood pressure cuff and an ECG chest strap (made of fabric) are put on. This is followed by an autonomic reactivity test (dive reflex). Here, an ice pack with a temperature of 4-6°C is placed centrally on the forehead for about 2 minutes. The effects of this stimulus on the heart action can be recorded in the ECG.
For genetic determination a blood sample is taken once (maximum 20 ml). These samples are given a number (pseudonymised), then will be frozen and analysed at the end of the study.
During the appointment, various questionnaires are also filled out on the patient's medical history, origin, lifestyle and how she/he deals with the death.
This is followed by a 10-minute concentration task on a PC and a short interview on past events of the study participant. This interview will last a maximum of 10 minutes, can be stopped at any time and represents the last part of the examination.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Bereavement, or having recently experienced the death of a significant person in one’s life, is rated as the most stressful life event and is associated to increased morbidity and mortality, known as the widowhood effect. The widowhood effect has been documented all over the world, across sex and age. One cause of the increase in mortality following bereavement is a major increase in cardiovascular risk. Two possible mechanisms linking bereavement stress and cardiovascular risk are vagal tone and inflammation. The present study aims to evaluate vagal tone and inflammation in a bereaved population, and to test whether an individual’s genetics increases the risk even further.
A cardinal candidate for a psychophysiological mechanism in humans is the vagus nerve. This nerve is a primary, fast and bidirectional route conveying physiological states to the brain (sensory fibers), as well as shaping and coordinating somatic response to adapt to environmental challenges (motor fibers). The central-peripheral brain-heart integration can be indexed non-invasively by cardiac autonomic activity using heart rate recordings. From heart rate, beat to beat variability can be calculated (i.e. heart rate variability (HRV)), representing a measure of autonomic function. Early bereavement is associated with increased 24-hour heart rate and lower HRV compared to controls. These two cardiovascular measures are both independent predictors of an increased risk of cardiovascular disease. In context of separation from a loved one, differences in the expression of the serotonin transporter (5-HTT) gene have been reported to moderate the level of HRV. Those findings raise the question of whether polymorphisms in the 5-HTT gene could also influence cardiovascular risk in recently bereaved adults.
In addition to cardiovascular variables, levels of circulating inflammatory mediators like Interleukin-6 (IL-6) are major risk factors for cardiovascular disease. Several studies have shown that IL-6 is an important mediator of atherosclerotic changes. This explains the role of IL-6 in coronary artery disease and is a connection between inflammation and cardiovascular risk. One allelic variation of the IL-6 gene is associated with higher circulating IL-6 levels in blood. Similar to the moderation by the serotonin genotype on HRV, IL-6 variations may moderate circulating IL-6 levels after stressful life events such as bereavement.
This study aims to clarify the moderating and interacting role of three genetic polymorphisms (5-HTTLPR; IL-174; IL-572) on cardiac vagal reactivity following a bereavement related and laboratory induced stressor in recently bereaved adults. Participants will undergo a control task (viewing nature pictures) and a stressor task (Separation Recall Interview) at the Clinic of Psychosomatic Medicine and Psychotherapy in Ulm, Germany.
The findings of the proposed study could help to recognize at-risk individuals (high-risk genetic predisposition to cardiovascular diseases after the loss of a loved person) and reduce morbidity and mortality in these persons through early preventative intervention following the experience of bereavement - a challenge nearly everyone is faced at least once in life.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00016597
  •   2019/04/11
  •   [---]*
  •   yes
  •   Approved
  •   416/18, Ethik-Kommission der Universität Ulm
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Effects of grief on the cardiovascular system
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Study procedure: The study consists of a circa 90-minute lab visit at the Clinic for Psychosomatic Medicine and Psychotherapy in Ulm. Potential study participants are women and men between 50 and 70 years who have lost a loved one (parent, sibling, spouse, child) in the last 6-24 months.
    After written consent, height and weight are measured and a blood pressure cuff and an ECG chest strap (made of fabric) are put on. This is followed by an autonomic reactivity test (dive reflex). Here, an ice pack with a temperature of 4-6°C is placed centrally on the forehead for about 2 minutes. The effects of this stimulus on the heart action can be recorded in the ECG.
    For genetic determination a blood sample is taken once (maximum 20 ml). These samples are given a number (pseudonymised), then will be frozen and analysed at the end of the study.
    During the appointment, various questionnaires are also filled out on the patient's medical history, origin, lifestyle and how she/he deals with the death.
    This is followed by a 10-minute concentration task on a PC and a short interview on past events of the study participant. This interview will last a maximum of 10 minutes, can be stopped at any time and represents the last part of the examination.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Non-interventional
  •   Observational study
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Basic research/physiological study
  •   Single (group)
  •   N/A
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Primary endpoint: change in vagal mediated cardiac autonomic activity as measured using Root Mean Square of Successive Differences (RMSSD) and High-Frequency Component (HFpower), moderated by 5-HTTLPR (5-Hydroxytryptamin transporter linked polymorphic region).

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

Plasma levels of Interleukin 6 (IL-6) - (moderated by IL-6 -174 & IL-6 -572, 5-HTTLPR (5-Hydroxytryptamin transporter linked polymorphic region))

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2019/04/12
  •   84
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   50   Years
  •   70   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

recently bereaved (defined as 6-24Month).

adults (aged 50-70 years), postmenopausal.

free of major medical illnesses (e.g., cancer, current major psychiatric disorder such as Major Depressive Disorder, substance dependence).

currently not using:
- Immunosuppressive medication
- Anticholinergic medication


end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

IL-6 levels larger 2 standard deviations above the mean, if there is self-reported illness two weeks prior to experimental assessments.
Medical non-compliance in context with chronic diseases (e.g. diabetes, rheumatoid arthritis).

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Klinik für Psychosomatische Medizin und Psychotherapie
    • Albert Einstein Allee 21
    • 89081  Ulm
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Klinik für Psychosomatische Medizin und Psychotherapie
    • Mr.  Dr.  Marc  Jarczok 
    • Albert Einstein Allee 21
    • 89081  ULM
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Klinik für Psychosomatische Medizin und Psychotherapie
    • Ms.  Dr. med.  Elisabeth  Balint 
    • Albert-Einstein-Allee 23
    • 89081  Ulm
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Klinik für Psychosomatische Medizin und Psychotherapie
    • Albert Einstein Allee 21
    • 89081  Ulm
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting stopped after recruiting started
  •   2020/03/15
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.