Impact of Post-ARDS Covid-19 Sedation on Persistent Neuroinflammation

NCT05233605 · tracked via the Priya Life Science France tracker

Sponsor

Assistance Publique - Hôpitaux de Paris

Phase

Observational

Started

2022-03-21

Last updated

2024-12-24

Condition(s) studied

Severe COVID-19

Study summary

ICU Patients admitted after ARDS due to COVID infection should be weaned from invasive mechanical ventilation as quickly as possible.

60% of ARDS patient after COVID infection admitted in ICU developp a delirium during mechanical ventilation weaning, serious event that can lead to death or acute and late complications since 30% of patients who had a delirium in ICU develop cognitive sequelae. Based on epidemiological arguments and mouse models, severe neuroinflammation is considered to be one of the physiopathological mechanisms causing delirium during ventilatory weaning.

In addition to its sedative properties, dexmedetomidine exhibits neuroprotective effects. In experimental models, dexmedetomidine reduces brain inflammation acting directly on the microglial phenotype. The role of this chronic neuroinflammatory condition on cognitive abilities and reserve begins to emerge in the literature no matter the initial stress is (surgery, head trauma, or Alzheimer's type dementia) and is therefore able to influence quality of life. The evaluation of this neuroinflammation by non-invasive tools appears essential in the management and follow-up of post-COVID cerebrolesed patients, as well as the potentially neuroprotective evaluation of dexmedetomidine.

Eligibility

Sex

ALL

Min age

18 Years

Max age

74 Years

Healthy volunteers

Inclusion Criteria: * Adult patient (age ≥ 18 years at the time of inclusion) under 75 years old * COVID-19 infection documented by PCR test performed on a nasopharyngeal swab or from a bronchoalveolar sample * High affinity homozygous TPSO genotyping for \[18F\] -DPA-714 or heterozygous intermediate affinity for \[18F\] -DPA-714 * Patient who was hospitalized in intensive care for ARDS after COVID infection which required mechanical ventilation and deep sedation for at least 24 hours * Patient alive at 24 months (+ 24 months) after discharge from intensive care * Signature of informed consent * Patient affiliated to a National French social security system, excluding (French) State Medical Aid (SMA) For the group of patients exposed to dexmedetomidine: * Administration of dexmedetomidine for at least 24 hours during intensive care hospitalization For the group of patients not exposed to dexmedetomidine: * No administration of dexmedetomidine during intensive care hospitalization Exclusion Criteria: * Protected adult (under legal protection, guardianship or curatorship) * Pregnancy or breast-feeding * Contraindication to PET or MRI examination * Severe renal impairment (creatinine clearance \<30 mL / min) * Contraindication to the administration of the radiopharmaceutical agent \[18F\]-DPA-714 * Serious neurological history at admission to intensive care: * Stroke * Severe head trauma * Dementia with loss of autonomy

Primary outcome measure(s)

Mean of SUVr of [18F]-DPA-714 in frontal lobes compared to cerebellar lobes — 24 months (+ 24 months) after ICU discharge
Persistent neuroinflammation is measured by \[18F\]-DPA-714 signal intensity obtained on PET-MRI imaging on the 2 frontal lobes (freesurfer segmentation, with signal intensity being the ratio of the measurement in the frontal lobes to that in the cerebellar lobes. The standard fixation will be expressed as an indexed value compared to the control value. The intensity of the \[18F\]-DPA-714 signal is the SUV (standard uptake value) or quantity of radioactivity fixed in the tissue which will be measured in each region of interest (frontal lobes and cerebellar lobes = reference) and related to the quantity of radioactivity injected for the examination. This signal will be corrected by taking into account the weight, the amount of radioactivity injected for the examination and the SNPrs6971 genotype (low, medium or high affinity of the radiotracer for its ligand). The ratio of SUV in the frontal lobes to the SUV of the cerebellar lobes

Trial sites (1)

Facility	City	Region	Status
Anesthesy department - Hôpital Pitié Salpêtrière	Paris	France	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05233605 on ClinicalTrials.gov ↗ ← All trials in France