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

April 11, 2025 updated by: Medical University Innsbruck

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Innsbruck, Austria
        • Medical University of Innsbruck

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Healthy controls
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 α-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.
Experimental: COVID-19 patients with olfactory dysfunction
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 α-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.
Experimental: COVID-19 patients without olfactory dysfunction
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 α-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.
Experimental: Patients with Parkinson's disease
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 α-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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Demonstration of ⍺-synuclein seeding activity in the OM (assessed by RT-QuIC) in subjects who recovered from COVID-19 compared to healthy controls.
Time Frame: 2 years
detection ⍺-synuclein seeding activity in olfactory mucosa of different patient groups
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University Innsbruck

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Beatrice Heim, MD PhD, Medical University Innsbruck

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 11, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 1, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 2, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 16, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1448/2020

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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