Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

COVID-19 Clinical Trial

Official title:

Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05650905
• Other study ID #: OPHT-180520
• Status: Recruiting
• Start date: July 26, 2021
• Est. completion date: December 31, 2023

Study information

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

Clinical Trial Summary

The Study objective is to measure retinal neurovascular coupling and blood flow parameters in patients previously infected with COVID-19, long COVID-19 and healthy age- and sex- matched control subjects

Description:

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting almost all countries in the world and because of its worldwide spread has been declared as pandemic in March 2020. While respiratory symptoms are the main manifestation of acute infection, there is also increasing evidence that neurological and vascular symptoms occur, and it is unknown whether residuals remain after patients have recovered. A recent report shows that changes in the human retina are even present one month after onset of symptoms. The eye, as an extension of the brain, offers the advantage that blood vessels as well as neural tissue can be visualized non-invasively in-vivo. Neurovascular coupling is the ability of neural tissue to adapt its blood flow to its metabolic demands, a phenomenon that does not only occur in the brain, but also in the retina. In the retina, neurovascular coupling can be studied by stimulating the retina with flicker light and measuring the response of the vessels. Retinal neurovascular coupling has been found to be impaired in diseases of the central nervous system (CNS) as well as in diseases associated with endothelial dysfunction. Since COVID-19 comes with CNS manifestations as well as endothelial dysfunction, we speculate that retinal neurovascular coupling might be impaired in patients even after they have recovered from COVID-19 infection. In the current study, retinal neurovascular coupling will be measured in patients who have recovered from COVID-19 infection with and without long COVID-19 and in healthy age- and sex-matched controls with no history of COVID-19 infection. In addition, retinal oxygen saturation, vessel diameters, vessel density as well as retinal and optic nerve head blood flow will be measured. To assess structural changes, measurement of central retinal thickness as well as retinal nerve fiber layer thickness will be performed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Inclusion criteria for healthy subjects

• Men and women aged over 18 years
• Non-smokers
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• No previous history of COVID-19 infection
• Negative testing for SARS-CoV-2 seroprevalence using nucleocapsid antibody tests
• Negative PCR test for SARS-CoV-2
• Normal ophthalmic findings, ametropy < 6 Dpt. Inclusion criteria for subjects with history of COVID-19 infection
• Men and women aged over 18 years
• Non-smokers
• History of COVID-19 infection (confirmed by a positive PCR test for SARS-CoV2 in the medical history) within the last 6 months
• Positive testing for SARS-CoV-2 seroprevalence using spike protein IgG antibody tests
• Negative PCR test for SARS-CoV-2 Inclusion criteria for subjects with long COVID-19
• Men and women aged over 18 years
• Non-smokers
• History of COVID-19 infection (confirmed by a positive PCR test for SARS-CoV2 in the medical history)
• Positive testing for SARS-CoV-2 seroprevalence
• Negative PCR test for SARS-CoV-2
• Long Covid according to the latest WHO-Guidelines Exclusion Criteria:

Any of the following will exclude a healthy control subject from the study:

• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• Presence or history of a severe medical condition as judged by the clinical investigator
• Participation in a clinical trial in the 3 weeks preceding the study
• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Pregnancy, planned pregnancy or lactatin
• History of epilepsia Any of the following will exclude a subject with history of COVID-19 infection from the

study:

• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Ametropy >6 Dpt
• Pregnancy, planned pregnancy or lactating
• History of epilepsia

Any of the following will exclude a subject with long COVID-19 from the study:

• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Ametropy >6 Dpt
• Pregnancy, planned pregnancy or lactating
• History of epilepsia
• Diabetes mellitus

Related Conditions & MeSH terms

• COVID-19
• Post-COVID-19 Syndrome

Intervention

Device:
• Dynamic Vessel Analyzer (DVA)
Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA
• Fourier domain optical coherence tomography (FDOCT)
Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT
• Optical coherence tomography (OCT)
Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT
• Laser Speckle Flowgraphy (LSFG)
Normalized blur and Relative flow volume will be assessed using the LSFG

Diagnostic Test:
• Proteomics and Metabolites in Plasma, tear fluid and finger sweat
Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Clinical Pharmacology	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Retinal neurovascular coupling	Retinal neurovascular coupling will be assessed using the DVA	Day 0
Secondary	Retinal vessel diameters	Retinal vessel diameters will be assessed using the DVA	Day 0
Secondary	Retinal oxygen saturation	Retinal oxygen saturation will be assessed using the DVA	Day 0
Secondary	Retinal blood velocities	Retinal blood velocities will be assessed using FDOCT	Day 0
Secondary	Retinal blood flow	Retinal blood flow will be assessed using FDOCT	Day 0
Secondary	Ocular perfusion pressure	Ocular perfusion pressure is going to be calulated	Day 0
Secondary	Retinal nerve fiber layer thickness	Retinal nerve fiber layer thickness will be assessed using OCT	Day 0
Secondary	Central retinal thickness	Central retinal thickness will be assessed using OCT	Day 0
Secondary	Retinal vessel density	Retinal vessel density will be assessed using OCT	Day 0
Secondary	Normalized blur	Normalized blur will be assessed using LSFG	Day 0
Secondary	Relative flow volume	Relative flow volume will be assessed using LSFG	Day 0
Secondary	Proteomics and Metabolites in Plasma	Proteomics and Metabolites in Plasma will be assessed through a Blood Sample	Day -14 to -1
Secondary	Proteomics and Metabolites in tear fluid	Proteomics and Metabolites in tear fluid will be assessed using Schirmer	Day 0
Secondary	Proteomics and Metabolites in finger sweat	Proteomics and Metabolites in finger sweat will be assessed using finger sweat filters	Day 0