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

• Conditions: Infection; Sepsis

• Registration Number: NCT05052203
• Lead Sponsor: Hjalmar Bouma

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-27
• Study First Submitted QC: 2021-09-10
• Study First Posted: 2021-09-22
• Study Start: 2021-09-28
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-10
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
DNA methylation (epigenetics) using the Illumina MethylationEPIC kit. Changes in DNA methylation at gene promoter/enhancer sites will be correlated through the NetworkAnalyst platform.	baseline versus 3 months follow up	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.
Gene expression (transcriptomics/qPCR) will be measured using the Illumina Hi-Seq instrument. Differential gene expression will be correlated through the NetworkAnalyst platform.	baseline versus 3 months follow up	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.

Secondary Outcome Measures

Name	Time	Method
Nutrition status measured with PS-SGA Short Form and SNAQ form. (both questionnaires)	3 months	study the association between epigenetic and transcriptomic signatures in sepsis and survivors with nutrition status. PS-SGA short form looks at weight loss, upper arm circumference, apetite and functionallity. PS-SGA short form scores weight, food intake, symptoms, activities and functionalilyti (nummeric; 0-52).
Sepsis severity defined with SOFA score	3 months follow up	study the association between severity of sepsis and the epigenetic and transcriptomic signatures in sepsis. SOFA scores will be available for patients admitted because of an infection.
Somatic symptoms (e.g. Patient Health questionnaire-15)	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with somatic symptoms. Patient Health Questionnaire-15 (PHQ-15; 0-30, minimal-high somatic symptom severity)
Mortality. Mortality status will be obtained from the Municipal Personal Records Database (BRP), containing reliable and complete registration all Dutch citizens	1 year	study the association between epigenetic and transcriptomic signatures and mortality in sepsis survivors and non-survivors and healthy controls. Mortality will be retrieved from the electronic health records (EHR) from the hospital and municipal registration. The cause of death will be retrieved from the EHR from the hospital, general practitioner and Dutch statistics' office (CBS).
Intoxications	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis survivors with intoxications. Information about intoxications will be retrieved from the electronic health records (EHR) from the hospital.
Medication use	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis survivors with medication use. Medication use will be retrieved from the electronic health records (EHR) from the hospital, general practitioner and pharmacy.
Physical activity (e.g. Short Questionnaire to Assess Health-Enhancing Activity) (SQUASH) and 'Utrechtse activiteiten lijst' (UAL))	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with physical activity
Activities of daily living as determined by EQ-5D-5L (if abnormal also Katz-ADL-6)	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with activities of daily living. EuroQol-5D (EQ5D; simple descriptive profile and a single index value for health status; higher values corresponding with better health) with visual analogue scale (VAS; 0-100, worse-best experienced health). Katz ADL-6 (0-6, fully dependent-independent)
Co-morbidity (a.o. Charlson comorbidity index)	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with comorbidity. Co-morbidity will be retrieved from the electronic health records (EHR) from the hospital, general practitioner and pharmacy. Data will be registered according to the Charlson' co-morbidity index (CCI; 1-2 mild co-morbidity, 3-4 moderate co-morbidity, 5 severe co-morbidity)
Length-of-stay in hospital/intensive care unit (ICU)	0-3 months	Length-of-stay in hospital and on intensive care unit (ICU) in days
Fatigue assessed with piper fatigue scale	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with fatigue.Piper Fatigue Scale-12 (PFS-12; 0-10, higher scores reflect more fatigue among four subscales (a) behavior, (b) affect, (c) sensory, (d) cognition)
Mood assessed with the Patient Health Questionnaire-2 ( (questionnaire)	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with mood. Patient Health Questionnaire-2 (PHQ-2; 0-6, higher score corresponds to reduced mental health)
Demographics	3 months	To study the association between epigenetic and transcriptomic signatures in sepsis survivors with demographics. Information about demograpics will be retrieved from the electronic health records (EHR) from the hospital.
Vital parameters	At baseline and three months.	Heart rate (bpm), blood pressure (mmHg), oxygen saturation (SpO2, SaO2, PaO2), breathing frequency (per min), consciousness (Glasgow coma scale), pain score (VAS), nausea/vomiting (y/n), defecation (y/n), urination (y/n), body weight (kg), length (cm), fluid balance (ml/day).

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands