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

NCT05233605 | Recruiting

• 2 other identifiers: APHP2004912020-004802-70
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Severe COVID-19

Keywords

SARS-Cov 2 (Severe Acute Respiratory Syndrome-Coronavirus 2); Covid-19; Dexmedetomidine; Neuroinflammation; [18F]-DPA-714; PET-MRI

Outcome Measures

Primary Outcomes (1)

• Mean of SUVr of [18F]-DPA-714 in frontal lobes compared to cerebellar lobes

  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

  24 months (+ 24 months) after ICU discharge

Secondary Outcomes (14)

• Neuro-cognitive lesions acquired using clinical assessment score means

  24 months (+24 months) after ICU discharge

• Neuro-cognitive lesions acquired using clinical assessment score means

  24 months (+24 months) after ICU discharge

• Neuro-cognitive lesions acquired using clinical assessment score means

  24 months (+24 months) after ICU discharge

• Neuro-cognitive lesions acquired using clinical assessment score means

  24 months (+24 months) after ICU discharge

• Neuro-cognitive lesions acquired using clinical assessment score means

  24 months (+24 months) after ICU discharge

Study Arms (2)

Exposed to Dexmedetomidine during ICU stay

Dexmedetomidine has been administered in accordance with its MA (at least 24 hours continuously with a starting dose of 0.7 µg/kg/h and then adjusted to sedation scores between 0.4 and 1.1 µg/kg/h), as part of care, prior to inclusion in the protocol

Not Exposed to Dexmedetomidine during ICU stay

Standard of care

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient admitted in ICU for COVID-19 ARDS and alive 2 years after infection

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Anesthesy department - Hôpital Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples (serum, blood mononuclear cells, total proteins for cytof, transcriptome and epigenome) will constitute biological collection

MeSH Terms

Conditions

COVID-19; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vincent DEGOS, Pr

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Central Study Contacts

Vincent DEGOS, Pr

CONTACT

(0)1 42 16 37 61; vincent.degos@aphp.fr

Laurence JALIN, Dr

CONTACT

(0)1 42 16 34 23; laurence.jalin@aphp.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: February 10, 2022
• Study Start: March 21, 2022
• Primary Completion: February 4, 2026
• Study Completion: February 4, 2026
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (1)