To study the long-term changes in DNA methylation and gene expression in sepsis survivors and their association with long-term morbidity and mortality after sepsis.
ID
Source
Brief title
Condition
- Other condition
- Infections - pathogen unspecified
Synonym
Health condition
sepsis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the current project is to measure changes in DNA
methylation (i.e. epigenetics) and gene expression (i.e. transcriptomics) of
blood leukocytes between sepsis survivors at ED admission and three months
after hospital discharge.
Secondary outcome
The secondary objectives are to correlate these changes with DNA methylation
and gene expression with clinical data of sepsis survivors including
post-sepsis syndrome symptoms (e.g. cognition, neuropsychiatric symptoms,
quality of life), cytometric and biochemical parameters that assess organ
function, rehospitalization frequency, and mortality, as well as the soluble
proteome and metabolome in blood to explore regulatory mechanisms. Lastly, we
will compare the DNA methylation and gene expression profile with the age and
sex-matched control group.
Background summary
Sepsis is a life-threatening dysregulated immune response to infection
associated with multi-organ failure and a high mortality rate.While researchers
have focused mainly on acute sepsis, post-sepsis care of survivors has long
been neglected despite the observation that many sepsis survivors suffer from
debilitating post-sepsis syndrome.This syndrome is characterized by frequent
hospital readmissions and increased mortality due to persistent immune
dysfunction, cardiovascular disease, and cognitive impairment, causing poor
quality of life and a substantial burden on the healthcare system.
Disconcertingly, the number of sepsis survivors at risk for hospital
readmission continues to rise. Of the post-sepsis symptoms, post-sepsis
immunosuppression is perhaps the most clinically important. While sepsis
presents as an initial phase of hyperinflammation (a *cytokine storm*), it is
followed by an immunosuppressive phase that is now understood to last weeks to
months and predisposes survivors to lethal secondary infections and sepsis
recurrence. A third of deaths eight years post-sepsis are caused by recurrent
sepsis. We hypothesize that changes in the transcriptome and DNA methylome in
immune cells of survivors might be the underlying driver for prolonged
immunosuppression, and may also be correlated with long-term morbidity and
mortality post-sepsis, as well as other symptoms of post-sepsis syndrome
including PTSD and cardiovascular disease.
Study objective
To study the long-term changes in DNA methylation and gene expression in sepsis
survivors and their association with long-term morbidity and mortality after
sepsis.
Study design
Observational longitudinal study with three-month follow up.
Study burden and risks
Participants already donated blood through a (minimally invasive) venipuncture
during their stay in the hospital for the Acutelines study. They will be asked
to donate blood as well after three months of hospital discharge. Control
subjects do not have to give blood after three months, as only the blood from
hospitalization will be used. To collect blood during follow-up, the study
participant will travel to the hospital where they will receive additional
clinical follow-up and treatment of possible comorbidities, which can be seen
as a minor benefit of joining this study.
Hanzeplein 1
Groningen 9713 AV
NL
Hanzeplein 1
Groningen 9713 AV
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria sepsis group:
- Adult patients, aged between 18 and 85 years
- Able to provide informed consent themselves or informed consent can be
obtained via next of kin or legal guardian
- Included in Acutelines, where blood sample were was drawn within 24 hours
upon of ED admission according to Acutelines protocol
- Satisfy the Sepsis-3 criteria for sepsis (Figure 2), combined with clinical
suspicion of infection and/or fever (body temperature > 38.5°C)
- Survive at 3 months post discharge
Inclusion criteria control group: adult patients, aged between 18 and 85 years
- Able to provide informed consent themselves or informed consent can be
obtained via next of kin or legal guardian
- Included in Acutelines, where blood sample was drawn upon ED admission
- Non-infectious reason of admission, specifically syncope, electrolyte
disturbance, intoxication, gastro-intestinal bleeding, undifferentiated
complaints
Exclusion criteria
- Transfer from another hospital
- Emergency room visit in connection with accidental exposure of bodily
material to patient ("needle stick injury")
- Visit an emergency room in connection with organ transplantation
- Discharged home without hospital admittance after ED visit
- Unable to give blood
- Immunosuppressive therapies such as corticosteroids (>10mg) or small molecule
immune suppressants within the last three months, or biologicals administered
within the last year
- Radiotherapy or systemic chemotherapy within the last three months
- Known pregnancy; the presence of pregnancy will be verified by asking the
potential participant
- A hospitalization of more than 21 days
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL76827.042.21 |