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NCT Number: NCT05867706

Caregiver Stress and Bereavement

The death of a spouse is considered one of the most stressful and impactful life events and is associated with increased morbidity and premature mortality. Early identification of individuals who are most at risk for poor health outcomes following bereavement is an important aim of precision medicine and disease prevention initiatives. A better understanding of caregiver burden and bereavement-related distress and its implication for health is a clinically-relevant step toward the development of treatments that improve health outcomes in bereaved spouses. This study aims to map profiles of individual differences in short- and long-term adjustment to loss, according to psychological (e.g., depression, stress, grief severity) and biological markers (e.g., inflammation, cortisol) over time.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University Hospital Zurich

Zurich, Canton of Zurich, 8091, Switzerland

Location status: Recruiting

Location contact

Annina Seiler

CONTACT

[email protected]

0041 44 255 9739

Annina Seiler

PRINCIPAL_INVESTIGATOR

About this study

The loss of a spouse is a highly impactful life event that places individuals at risk for mental and physical health problems. Particularly in the immediate weeks and months after the loss, bereavement is associated with a significantly increased risk of multimorbidity and mortality, including elevated inflammation, cardiovascular diseases and some cancers. Grief is a typical reaction to the loss of a significant person and is characterized by symptoms of intense distress, anxiety, yearning, longing, and sadness, all of which generally subside over time. There is considerable variability in how people respond to bereavement. Although the vast majority of bereaved individuals show resilience against loss and adjust adequately without professional psychological support, 10% - 20% of bereaved individuals develop intense and prolonged grief reactions.

The field of psychoneuroimmunology has contributed considerably to our understanding of the effect of stress on the psyche, as well as on the nervous, immune, and endocrine systems. Stressful life events, and the negative emotions they provoke, can induce low-grade inflammation through several autonomic, neuroendocrine, and neuroimmune pathways, which in turn suppress the effectiveness of the immune system, and thereby, increase vulnerability to physical and mental health problems across a person's lifespan. Bereavement is a highly-stressful event, which triggers biological responses via several autonomic, endocrine, and inflammatory mechanisms. Growing evidence suggests that the health consequences of caregiving for terminally-ill patients and bereavement after the loss of a spouse are associated with a wide spectrum of neuroendocrine factors and immunologic and inflammatory markers. Low-grade systemic inflammation, as reflected by elevated concentrations of cytokines (e.g., C-reactive protein, CRP; interleukin 6, IL-6; tumor necrosis factor alpha, TNF-a) is a robust risk factor for the onset of many diseases, including major depression, cardiovascular disease, and stroke.

The caregivers' burden and needs are often not a hospital's priority and overlooked. Yet, the health consequences of caring for a terminally-ill spouse, as well as the need for follow-up care programs for caregivers of a deceased spouse are not well understood. Acknowledging that bereavement-related changes in immune function could account considerably for an increased risk of morbidity and mortality in bereaved individuals, the identification of biobehavioral mechanisms that can be modified or targeted early is an important and clinically-relevant step toward the development of treatments that improve health outcomes in bereaved individuals.

The proposed study is based on the Social Signal Transduction Theory of Depression (Slavich et al.), which suggests that early life stress exposure can shape an individual's neuro-inflammatory sensitivity to stress to later- occurring threats or acute adverse life events, and thereby increase their vulnerability to physical and mental health problems across the lifespan.

The study's aims are two-fold: 1) to map profiles of individual differences in long-term adjustment to loss, according to psychological and biological markers over time; and 2) to examine whether cumulative lifetime stress exposure and neuro-inflammatory sensitivity to stress moderate the association between an acute stressful life event (i.e., the loss of a terminally-ill spouse after a long period of intensive caregiving) and the spouse's health outcomes following bereavement and, thereby, explain individual differences in resilience.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant age ≥ 18 years
  • Caregiver or spouse of a patients suffering from a terminal illness (estimated life expectancy ≤ 6 months),
  • regarded as the patients primary caregiver (i.e., intimately involved in care of the patient since time of the diagnosis, looking after his/her daily needs, supervising the medications, bringing the patient to the hospital, staying with the patient during inpatient stay, and maintaining liaison with the hospital staff),
  • German as primary language
  • signed informed consent.

Exclusion criteria

  • Significant visual or auditory problems, cognitive impairment,
  • morbid obesity (body mass index ≥40 kg/m2,
  • alcohol or drug abuse
  • active malignancy
  • severe illness (respiratory, heart, liver and renal failure)
  • major medical conditions involving the immune system (e.g., diabetes type 1 or 2, autoimmune and/ or inflammatory diseases including rheumatoid arthritis and ulcerative colitis, asthma, thyroid diseases)
  • severe hypertension (>200/120 mmHg)
  • regular use of medication with major immunological consequences (e.g., corticosteroids, immunosuppressive therapy)
  • pregnant or breast-feeding

Treatment and study plan

Primary outcomes

  1. The Center for Epidemiological Studies Depression Scale (CES-D)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Depression

  2. interleukine-6 (IL-6)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Measure of inflammation

Secondary outcomes

  1. The Stress and Adversity Inventory (STRAIN)

    Time frame: Assessment 1: 6 months before patient's death

    Adverse life experiences

  2. Physical Health Questionnaire (PHQ-D)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Physical Health

  3. Charlson Comorbidity Index (CC)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Comorbidities

  4. The Perceived Stress Scale (PSS)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Stress

  5. The RAND 12-Item Short Form Health Survey (SF-12)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Quality of Life

  6. Pittsburg Sleep Quality Index (PSQI)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Sleep quality

  7. PTSD Checklist for DSM-5 (PCL-5)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    PTSD symptoms

  8. Dissociative Subtype of PTSD Scale (DSPS)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Dissociative symptomes

  9. Cognitive Processing Questionnaire (CPQ)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Cognitive Processing

  10. The Inventory of Complicated Grief (ICG)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Complicated grief

  11. Prolonged Grief Reaction (PG13+9)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    Prolonged grief

  12. heart-rate/heart-rate variability

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    physiological stress marker

  13. nail cortisol and cortisone

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    nail cortisol and cortisone

  14. tumor necrosis factor alpha (TNF-a)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    measure of inflammation

  15. C-reactive protein (CRP)

    Time frame: Assessment 1: 6 months before patient's death; Assessment: 3-6 months post-loss; Assessment: 9-12 months post-loss

    measure of inflammation

Study contacts

Contact information is provided by the study sponsor or research team.

Annina Seiler, PD PhD

CONTACT

[email protected]

+41 43 253 04 02

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Collaborators

  • University of California
  • University of Salzburg

Registry information

Official study title

The Psychobiological Adjustment to Bereavement Among Cancer Caregivers

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
May 22, 2023
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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