COVID-19 and Brain: Cognition and Mental Health

COVID-19 Clinical Trial

— DIANA  

Official title:

COVID-19 and Brain: Cognition and Mental Health

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05307549
• Other study ID #: 2020PANDE00053
• Status: Completed
• Start date: May 14, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2022
• Source: University of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The main goal of DIANA is to investigate the potential discriminative power of multimodal biomarkers in COVID adverse outcomes. The study of the neuropathological underlying mechanisms in COVID from a translational approach at: (1) the behavioural-clinical level from cognitive, emotional and functional data; (2) the brain connectome level from structural and functional imaging data; and (3) biogenetic level from blood and stool data. Moreover, the investigators will develop machine learning based predictive models of cognitive, mental health, functionality, and brain connectivity evolution in post-COVID syndrome patients.

Description:

DIANA project is an observational, descriptive, and cross-sectional study in which participants will not be randomized. Case people (adult survivors of severe COVID-19 N=134) will compare to healthy adult controls (n=66). It is a multicentric study where all the participants will be recruited from eleven Catalan public health institutions. The participants will be assessed on cognitive, emotional and functional status. The investigators will obtain a blood sample to study inflammation, vascular risk, growth factors, angiogenesis, neurogenesis, and cellular metabolism biomarkers and genes, and a stool sample for gut microbiota study. Structural and functional MRI will be performed on a subgroup of participants 40 COVID-19 survivors and 40 healthy controls.

The objectives of the project are:

1. To examine the impact of the COVID-19 illness on cognition, emotion/behavior, and functionality.

2. To examine the possible affectation in brain grey and white matter and functional connectivity of severe forms COVID-19 survivors.

3. To relate demographic characteristics, previous pathologies, lifestyle, baseline cerebral status, genetic polymorphism, and clinical data in acute illness with cognitive, mental health, functionality, and brain connectivity outcomes of severe forms COVID-19 survivors.

4. To study the post-COVID-19 biomarkers of inflammation, vascular risk, growth factors, angiogenesis, neurogenesis, and cellular metabolism and its relationship with the cognitive, mental health, functionality, and brain connectivity outcomes of severe forms COVID-19 survivors.

5. To quantify the presence of different bacterial species in the post COVID stool sample and analyze the wealth and diversity of the diverse populations. To study if these values are related to the performance of neuropsychological and behavioral tests and neuroimaging data.

6. - To develop machine learning based predictive models of cognitive, mental health, functionality and brain connectivity evolution in post COVID 19 survivors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 31, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Post-COVID Group:

Inclusion Criteria:

• Confirmed diagnosis of COVID-19 according to WHO interim with signs and symptoms of the severe disease during the acute phase

• Presence of cognitive complaints after COVID-19 diagnosis

• Participants have to be discharged from the hospital at least three months before inclusion

• Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki

Exclusion Criteria:

• Participants have symptoms of delirium according to Delirium Rating Scale-revised 98

• Established diagnosis before COVID-19 disease of psychiatric, neurological, neurodevelopmental disorder or systemic pathologies are known to cause cognitive deficits

• Motor or sensory alterations that impede the neuropsychological examination

• Participants with a metal prosthesis (for MRI studies)

• Subjects suffering from claustrophobia or requiring sedation due to high anxiety (for MRI studies)

Healthy Adult Control group

Inclusion Criteria

• Healthy people who have not had COVID-19

• Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki

Exclusion criteria: the same as COVID-19 survivors

Related Conditions & MeSH terms

• COVID-19

Locations

Country	Name	City	State
Spain	University of Barcelona	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
University of Barcelona	Consorci Sanitari de Terrassa, Universitat Politècnica de Catalunya

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences between groups in auditory attention	Auditory attention is measured with Digit Span Forward. Participants are asked to repeat numbers in the same order as read aloud by the examiner. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in working memory	Working memory is measured with Digit Span Backward. Participants are asked to repeat the numbers in the reverse order of that presented by the examiner. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in language	Language is measured with the Boston Naming Test. It consists of 60 line drawings of objects of graded difficulty, ranging from very common things to less familiar objects. The total score is the sum of correct answers. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in verbal memory	Verbal memory is measured with the Auditory Verbal Learning Test (AVLT). It is a word-learning test where five presentations of a 15-word list are given, each followed by an attempted recall. This is followed by a second 15-word interference list (list B), followed by recall of list A. Delayed recall and recognition are also tested. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in visual memory	Visual memory is measured with the Rey-Osterrieth Complex Figure (ROCF) test. The participants are asked to copy complex geometric shapes and then reproduce them from memory. A delayed recall is also tested. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in psychomotor speed	Processing speed is measured with Coding subtest of WAIS. Participants are asked to use a key to put in the appropriate symbols for a list of numbers. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in perceptual reasoning	Perceptual reasoning is measured with Matrix reasoning subtest of WAIS. Participants are asked to choose which of some possible options the missing picture is from matrix of abstract pictures. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in executive function	A composite score is made with the z-scores of phonemic (sum of the three letters) and semantic fluency, Trail Making Test B (time) and STROOP test (color-word interference total items in 120 seconds).	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in social cognition	Social cognition is measured with the Reading the Mind in the Eyes Test. Participants are asked to choose the emotional state that best describes the eyes, choosing between one of four possible emotions in the 36 photographs of male and female eyes depicting emotional states. Higher scores mean a better outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in anxiety	Anxiety is measured with the 7-item Generalized Anxiety Disorder Scale (GAD-7), a Likert-type scale with questions ranging from "not at all" (0 points) to "nearly every day" (3 points). The maximum score is 24. Higher scores mean a worse outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in depression	Depression is measured with the Patient Health Questionnaire-9 (PHQ-9) which scores each of the 9 DSM-IV criteria as "not at all" (0 points) to "nearly every day" (3 points). Higher scores mean a worse outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Primary	Differences between groups in Post-traumatic Stress Disorder	Post-Traumatic Stress Disorder is measured with The Post-Traumatic Stress Disorder Checklist (PCL-5), a 20-item questionnaire corresponding to the DSM-5 symptom criteria for PTSD, which scores each criterion as "not at all" (0 points) to "extremely" (4 points). The ratings of items are added together to calculate the total score (range=0-80). Higher scores mean a worse outcome.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in Fatigue	Fatigue is measured with the Chalder Fatigue Scale, an 11-item questionnaire measuring the severity of physical and mental fatigue on two separate subscales. Seven items represent physical fatigue (items 1-7) and 4 represent mental fatigue (items 8-11). Each item " less than usual" (0) to " much more than usual" (3). The ratings of items are added together to calculate the total score (range=0-33). High scores represent high levels of fatigue.	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in Quality of Life	Quality of life is measured with a 12-item World Health Organization Disability Assessment Schedule-II (WHODAS-II). Patients are asked to state the level of difficulty experienced, considering how they usually do the activity. The scale scores each item as "none" (1) to "cannot do" (5). The total score is calculated with an SPSS syntax, and the range varies from 0 to 100, with higher scores reflecting more significant disability.; (WHODAS-II)	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in White Matter integrity	White matter integrity: tractography measured by MRI	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in brain Volumetry	Grey and white matter volume measured by MRI	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in Resting-state connectivity	Resting state brain activity using fMRI	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic Interleukin- 6 (IL-6)	The plasma levels of IL-6 are measured with enzyme-linked immunosorbent assay (ELISA) Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic D-Dimer	The plasma levels of D-Dimer are measured with ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic Nerve Growth Factor (NGF)	The plasma levels of NGF are measured with ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic Glial Fibrillary Acidic Protein (GFAp)	The plasma levels of GFAp are measured with ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic NT-proB-type Natriuretic Peptide (BNP)	The plasma levels of BNP are measured with ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic lipid peroxidation products	The plasma levels of malondialdehyde are measured with TBARS assay method	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic Thrombomodulin	The plasma levels of Thrombomodulin are measured with ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic Endothelin 1	The plasma levels of Endothelin 1 are measured with ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic Ferritin	The plasma levels of Ferritin are measured with biochemical assay	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in plasmatic C-Reactive Protein (CRP)	The plasma levels of CRP are measured with high sensitivity c-reactive protein ELISA Kit	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary	Differences between groups in Microbiota data	Bacterial composition of stool samples in terms of relative abundance	At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19