Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis

NCT05052203 | Unknown DMC

• 1 other identifier: 202100108
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.7 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.

Conditions

Sepsis; Infection

Keywords

Post sepsis syndrome; Epigenetic; Transcriptome; Recovery

Outcome Measures

Primary Outcomes (2)

• DNA methylation (epigenetics) using the Illumina MethylationEPIC kit. Changes in DNA methylation at gene promoter/enhancer sites will be correlated through the NetworkAnalyst platform.

  The primary objective of the current project is to measure changes in DNA methylation (i.e. epigenetics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge.

  baseline versus 3 months follow up

• Gene expression (transcriptomics/qPCR) will be measured using the Illumina Hi-Seq instrument. Differential gene expression will be correlated through the NetworkAnalyst platform.

  The primary objective of the current project is to measure changes in gene expression (i.e. transcriptomics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge.

  baseline versus 3 months follow up

Secondary Outcomes (14)

• Nutrition status measured with PS-SGA Short Form and SNAQ form. (both questionnaires)

  3 months

• Mortality. Mortality status will be obtained from the Municipal Personal Records Database (BRP), containing reliable and complete registration all Dutch citizens

  1 year

• Demographics

  3 months

• Intoxications

  3 months

• Medication use

  3 months

Interventions

Exposure of interest: study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytes OTHER

The primary objective is to study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients between 18-85 years old admitted to the emergency department (ED) of the University Medical Center Groningen (UMCG) with suspected sepsis according to the sepsis-3 criteria who survive their ED admission at three months. A control group will compose of age and sex-matched ED patients admitted for non-infectious causes. Both the septic patients and controls have already been enrolled in the Acutelines study.

You may qualify if:

• 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
• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hjalmar Bouma: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

MeSH Terms

Conditions

Sepsis; Infections

Interventions

Epigenesis, Genetic; Gene Expression; Gene Expression Profiling; Leukocyte Count

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gene Expression Regulation; Genetic Phenomena; Genetic Techniques; Investigative Techniques; Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Internist and Research Fellow

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 22, 2021
• Study Start: September 28, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)