Longitudinal Evolution of Biomarkers of Dysautonomia and Inflammation During Sepsis in Children

Sepsis Clinical Trial

— DysREAped  

Official title:

Longitudinal Evolution of Biomarkers of Dysautonomia and Inflammation During Sepsis in Children - An Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05807555
• Other study ID #: 22CH528
• Secondary ID: 2022-A02587-36
• Status: Recruiting
• Start date: March 29, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: May 2024
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: HUGUES PATURAL, MD-PHD
• Phone: (0)4 77 82 85 42
• Email: hugues.patural[@]chu-st-etienne.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The Autonomic Nervous System (ANS) regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. Many studies have investigated induced stimulation of the vagus nerve and its therapeutic effect in inhibiting TNFα (Tumor Necrosis Factor alpha) secretion, and therefore the risk of hypotension, septic shock, organ dysfunction during inflammation. While the anti-inflammatory effect of the autonomic nervous system on inflammation has been well studied, conversely, the effect of major inflammation on the balance of the autonomic nervous system is more difficult to understand. The inflammatory reflex could be overwhelmed and the regulatory centers of the brainstem dysregulated during situations of extreme inflammation.

Description:

The purpose of this study is to follow the short-term evolution of sympathetic and parasympathetic markers of dysautonomia in children hospitalized in intensive care units for severe sepsis, to characterize the evolution of the different autonomic indices according to the site of infection (meningitis, pulmonary infection, organ failure, bacteraemia) and types of pathogens (viral, bacterial, atypical germs) and correlating the evolution of the various inflammation biomarkers and cytokines with the degree of dysautonomia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 17 Years

Eligibility

Inclusion Criteria for cases group :

• Hospitalization in a pediatric intensive care unit.
• Presenting the sepsis criteria
• Patient affiliated or entitled to a social security scheme
• Holders of parental authority having received informed information about the study and having signed the consent form

Exclusion Criteria for cases group :

• Parents or legal guardians who do not speak French
• Chronic or acute pathology that can alter autonomic balance (congenital heart disease, encephalopathy, neuropathy, acute pain, etc.)
• Recent general anesthesia less than 48 hours old. (inclusion may be made beyond 48 hours from the last general anesthesia if the inclusion criteria remain present)
• Taking treatments that can alter the ANS (ß-blockers, etc.) or inflammation (NSAIDs, corticosteroids)

Inclusion criteria for control group :

• Patient affiliated or entitled to a social security scheme
• Holders of parental authority having received informed information about the study and having signed the consent form

Exclusion Criteria for control group :

• Parents or legal guardians who do not speak French
• Chronic or acute pathology that can alter autonomic balance (congenital heart disease, encephalopathy, neuropathy, acute pain, etc.)
• Recent general anesthesia less than 1 month.
• Taking treatments that can alter the ANS (ß-blockers, etc.) or inflammation (NSAIDs, corticosteroids)

Related Conditions & MeSH terms

• Autonomic Nervous System
• Autonomic Nervous System Diseases
• Inflammation
• Primary Dysautonomias
• Sepsis
• Toxemia

Intervention

Other:
• Ambulatory ECG
24h ECG monitoring

Biological:
• Blood sample
The usual biological tests necessary for the management of the child and the addition of 1 tube of 2 ml

Locations

Country	Name	City	State
France	Chu de Saint-Etienne	Saint-Étienne

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kinetic of the HF(High Frequency) index (ms2/Hz) of heart rate variability	Measure of the HF index of heart rate continuously at the patient's bed, during a quiet sleep phase at night, day by day for the entire duration of hospitalization in the ICU.	Through discharge from the ICU, an average of 15 days
Secondary	Global activity indices (SDNN (Standard deviation of the NN (R-R) intervals) evaluation	Measured continuously in quiet sleep at night, by temporal, geometric, frequency, fractal and entropy analysis	Through discharge from the ICU, an average of 15 days
Secondary	Plot (Poincaré plot)) evaluation	Measured continuously in quiet sleep at night, by temporal, geometric, frequency, fractal and entropy analysis	Through discharge from the ICU, an average of 15 days
Secondary	Parasympathetic indices (pNN50 (Percentage of successive RR intervals that differ by more than 50 ms) evaluation	Measured continuously in quiet sleep at night, by temporal, geometric, frequency, fractal and entropy analysis	Through discharge from the ICU, an average of 15 days
Secondary	Parasympathetic indices RMSSD (Root mean square of successive RR interval differences) evaluation	Measured continuously in quiet sleep at night, by temporal, geometric, frequency, fractal and entropy analysis	Through discharge from the ICU, an average of 15 days
Secondary	Parasympathetic indices HF (High Frequency) evaluation	Measured continuously in quiet sleep at night, by temporal, geometric, frequency, fractal and entropy analysis	Through discharge from the ICU, an average of 15 days
Secondary	Sympathetic indices (LF, LF/HF ratio) evaluation	Measured continuously in quiet sleep at night, by temporal, geometric, frequency, fractal and entropy analysis	Through discharge from the ICU, an average of 15 days
Secondary	Evolution of biological markers of inflammation: CRP (C-reactive protein) (mg/L)	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Evolution of biological markers of inflammation : Procalcitonin (ng/mL)	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Evolution of biological markers of inflammation : Leukocytes (G/L)	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Evolution of biological markers of inflammation : Ferritin (µg/L)s	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Evolution of biological markers of inflammation : Fibrinogen (g/L)	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Evolution of biological markers of inflammation : Platelets (G/L)	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Evolution of biological markers of inflammation : Triglycerides (g/L)	Collection of blood sampling for analysis	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Interferon alpha, interferon beta and interferon gamma.	Analysed by Luminex from blood sample (pg/mg)	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Tumor Necrosis Factor (TNF)	Analysed by Luminex from blood sample (pg/ml)	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Interleukines (IL1, IL2, IL3; IL4, IL5, IL6, IL7, IL8, IL9, IL10, IL11, IL12, IL13)	Analysed by Luminex from blood sample (pg/ml)	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Presence or absence of virus in blood	PCR (Polymerase chain reaction) multiplex	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Presence or absence of bacteria in blood	Blood cultures	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Presence or absence of bacteria in bone-marrow	Lumbar puncture	Day : 1, at discharge from the ICU, an average of 90 days
Secondary	Presence or absence of bacteria in urine	cytobacteriological examination of urine	Day : 1, at discharge from the ICU, an average of 90 days