Neurotropism and Neuroinflammation in COVID-19 Patients With Delirium.

Covid19 Clinical Trial

— BRAINSTORM  

Official title:

SARS-CoV-2 Neurotropism, micRoglial ActivatioN and Cytokine dySregulaTiOn in COVID-19 Patients With Delirium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04785157
• Other study ID #: RC31/20/0441
• Secondary ID: 2020-005827-35
• Status: Completed
• Start date: June 1, 2021
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2023
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Emerging evidence indicates that SARS-CoV-2, the etiologic agent of COVID-19, can cause neurological, neuropsychological and psychiatric complications. Given the global dimensions of the current pandemic, there is to consider the possible large-scale neurocognitive impact of COVID-19. Therefore, there is an urgent need for longitudinal studies to determine the acute and chronic effects that COVID-19 may have on the Central Nervous System. These putative effects include the possibility that the CNS serves as a reservoir for the virus, and that COVID-19 triggers CNS deleterious inflammatory cascades and neurodegenerative process. The public implications of these effects are very important in the long term.

Description:

The BRAINSTORM project aims at creating a proof-of-concept dataset from severe COVID-19 patients with delirium. For the first time, this longitudinal study will rely on repeated and concomitant: i) SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF), ii) systemic and central immune response characterization, associated to the assessment of CNS damage biomarkers (peripheral blood and CSF), iii) in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia), iv) structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity), v) multi-domains neurocognitive assessment. This dataset will be made FAIR to allow open data use and to prepare future studies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (male or female > or = 18 years)

• COVID-19 (positive respiratory track PCR test < 30 days)

• Delirium (CAM-ICU criteria)

• informed and written consent to participate in the study by patient's surrogate.

Exclusion Criteria:

• medical decision of withdrawal of life sustaining treatments previous to patients recruitment

• former neurological or psychiatric disability

• MRI or PET scan contraindication

• pregnancy

• hemodynamic or respiratory failure precluding patient's transport / MRI or PET scanning

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Delirium
• Post-traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Biological:
• serology testing profiles description
SARS-CoV-2 quasispecies detection and associated serology testing profiles description (peripheral blood and cerebrospinal fluid - CSF)
• immune response characterization
systemic and central immune response characterization , associated to the assessment of CNS damage biomarkers (peripheral blood and CSF)

Other:
• in vivo brain PET-TSPO acquisitions
in vivo brain PET-TSPO acquisitions (Positon Emission Tomography using a radioligand that targets the Translocator Protein, which is upregulated in activated microglia)
• brain MRI assessment
structural/functional brain MRI assessment (PWI/DWI mismatch imaging, quantification of gray and white matter microstructural integrity, DTI, functional connectivity)

Behavioral:
• neurocognitive assessment
multi-domains neurocognitive assessment

Locations

Country	Name	City	State
France	University Hospital of Toulouse	Toulouse
France	CHRU Tours	Tours

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PET imaging examination	Intensity and topography of [18F]DPA-714-labeled microglial activation in vivo in PET imaging examination	Day 0
Primary	PET imaging examination	Intensity and topography of [18F]DPA-714-labeled microglial activation in vivo in PET imaging examination	Month 3
Secondary	SARS-CoV-2 quasispecies detection in acute delirium phase in blood specimen	SARS-CoV-2 quasispecies detection in blood specimen	Day 0
Secondary	SARS-CoV-2 quasispecies detection 3 month after the acute delirium phase in blood specimen	SARS-CoV-2 quasispecies detection in blood specimen	Month 3
Secondary	SARS-CoV-2 quasispecies detection in acute delirium phase in cerebrospinal fluid specimen	SARS-CoV-2 quasispecies detection in cerebrospinal fluid specimen	Day 0
Secondary	SARS-CoV-2 quasispecies detection 3 month after the acute delirium phase in cerebrospinal fluid specimen	SARS-CoV-2 quasispecies detection in cerebrospinal fluid specimen	Month 3
Secondary	multimodal MRI in acute delirium phase	Imaging criteria: Structural-functional disconnects at the whole brain level (multimodal MRI)	Day 0
Secondary	multimodal MRI 3 months after the acute delirium phase	Imaging criteria: Structural-functional disconnects at the whole brain level (multimodal MRI)	month 3