α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19

COVID-19 Clinical Trial

Official title:

α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19 - A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05401773
• Other study ID #: 1448/2020
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2022
• Source: Medical University Innsbruck
• Contact: Beatrice Heim, MD PhD
• Phone: +43 512 504 81128
• Email: beatrice.heim[@]tirol-kliniken.at; beatrice.heim[@]i-med.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Loss of the sense of smell is a characteristic feature of COVID-19 and likely related to viral invasion of the olfactory mucosa but is also a prodromal feature of PD. This constellation has kindled concerns that COVID-19 - similar to the Spanish Flu Pandemic in 1918 - might trigger a second wave of post-infectious parkinsonism. The main objective of the study is to probe for the presence of pathological α-synuclein assemblies in the olfactory mucosa of patients with COVID-19.

Description:

Deposits of misfolded proteins are the cause of frequent neurological diseases such as Alzheimer's or Parkinson's disease. In Parkinson's disease, the misfolded protein alpha-synuclein is found in the olfactory mucosa of the nose, which contains nerve cells responsible for smell perception, from which the misfolded alpha-synuclein spreads further into the brain. The mechanisms that lead to this misfolding and the resulting damage to the nervous system are still unclear. One hypothesis is that inflammatory processes such as viral infections trigger the misfolding of alpha-synuclein in Parkinson's disease and can lead to its deposition. Based on this assumption and the striking involvement of the sense of smell in SARS-CoV-2 infection (COVID-19), the aim of this study is to investigate the olfactory epithelium of the nasal mucosa of COVID-19 patients for possible alpha-synuclein deposits by using nasal swabs. We hypothesize that the invasion of olfactory neurons and subsequent inflammatory responses could trigger α-synuclein misfolding and aggregation. Therefore, we aim to investigate for the presence of α-synuclein seeding activity in the olfactory mucosa of subjects who have recovered from COVID-19 by using Real-time Quaking-Induced Conversion (RT-QuIC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Participants must be 18 years or older;

2. Participants are able to understand the aim of the study and the planned procedures;

3. Written informed consent form;

4. Participants fulfilling the criteria for one of the following groups:

1. COVID-19 patients with OD:

• Prior history of COVID-19 (clinical documentation plus corresponding positive PCR test) at least 3 months ago;
• OD (Sniffin' sticks discrimination and identification both <13/16 items correct) persisting for at least 3 months after SARS-CoV-2 infection;
• Negative antigen test on day of study inclusion;
• No evidence of structural nasal pathologies possibly responsible for OD.

2. COVID-19 patients without OD:

• Prior history of COVID-19 (clinical documentation plus corresponding positive PCR test) at least 3 months ago;
• No history of/current OD (Sniffin' sticks discrimination and identification both >12/16 items correct);
• Negative antigen test on day of study inclusion.

3. Healthy Controls:

• No history of COVID-19 and negative SARS-CoV-2 antibody test unless subject is vaccinated;
• Negative antigen test on day of study inclusion;
• No history of OD;
• Subjective and objective normal olfactory function (Sniffin' sticks discrimination and identification both >12/16 items correct). 10 Application for Clinical Research

4. Patients with Parkinson's disease (n = 50):

• Confirmed diagnosis of PD according to diagnostic criteria.
• No history of COVID-19 and negative SARS-CoV-2 antibody test unless subject is vaccinated;
• Negative antigen test on day of study inclusion;

Exclusion Criteria:

1. Patients:

• History of OD prior to SARS-CoV-2 infection;
• Pre-existent relevant neurological disorder;
• Positive SARS-CoV-2 antigen test on day of study inclusion;
• Patients with OD only: structural pathology possibly responsible for OD.

2. Healthy controls:

• Pre-existent relevant neurological disorder;
• History of/presence of olfactory dysfunction (Sniffin' sticks discrimination and identification both <13/16 items correct);
• Positive SARS-CoV-2 antigen test on day of study inclusion;
• Positive SARS-CoV-2 antibody test unless subject is vaccinated.

3. Patients with Parkinson's disease:

• History of COVID-19;
• Positive SARS-CoV-2 antigen test on day of study inclusion;
• Positive SARS-CoV-2 antibody test unless subject is vaccinated.

Related Conditions & MeSH terms

• COVID-19

Intervention

Other:
• Real-time Quaking-Induced Conversion (RT-QuIC)
RT-QuIC is increasingly used as diagnostic tools in synucleinopathies and has shown high sensitivity and specificity for the detection of a-synuclein seeds in CSF and tissue samples, including the olfactory mucosa in different patients' cohorts including Parkinson's patientients, patients with REM sleep behavior disorder (RBD), and patients with dementia with Lewy bodies.

Locations

Country	Name	City	State
Austria	Medical University of Innsbruck	Innsbruck

Sponsors (1)

Lead Sponsor	Collaborator
Medical University Innsbruck

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demonstration of ?-synuclein seeding activity in the OM (assessed by RT-QuIC) in subjects who recovered from COVID-19 compared to healthy controls.		1 year