α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19 - A Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Demonstration of ⍺-synuclein seeding activity in the OM (assessed by RT-QuIC) in subjects who recovered from COVID-19 compared to healthy controls.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- 观察性
- 观察模型
- 病例对照
- 时间视角
- 前瞻性
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- Participants must be 18 years or older;
- Participants are able to understand the aim of the study and the planned procedures;
- Written informed consent form;
- Participants fulfilling the criteria for one of the following groups:
- 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.
- 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.
- 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
- 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;
- COVID-19 patients with OD:
排除标准
- 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.
- 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.
- 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.
研究组 & 干预措施
COVID-19 patients with olfactory dysfunction
COVID-19 patients with olfactory dysfunction
干预措施: Real-time Quaking-Induced Conversion (RT-QuIC) (Other)
COVID-19 patients without olfactory dysfunction
COVID-19 patients without olfactory dysfunction
干预措施: Real-time Quaking-Induced Conversion (RT-QuIC) (Other)
Healthy controls
Healthy controls
干预措施: Real-time Quaking-Induced Conversion (RT-QuIC) (Other)
Patients with Parkinson's disease
Patients with Parkinson's disease
干预措施: Real-time Quaking-Induced Conversion (RT-QuIC) (Other)
结局指标
主要结局
Demonstration of ⍺-synuclein seeding activity in the OM (assessed by RT-QuIC) in subjects who recovered from COVID-19 compared to healthy controls.
时间窗: 2 years
detection ⍺-synuclein seeding activity in olfactory mucosa of different patient groups
次要结局
未报告次要终点
研究者
研究点 (1)
标识符
- NCT 编号
- NCT05401773
- 其他研究编号
- 1448/2020
日期
- 首次提交
- (4年前)
- 首次发布
- (4年前)
- 主要完成日期
- (去年)
- 研究完成日期
- (去年)
- 最近核实
- (去年)
- 最近更新
- (前天)
监管与共享
- FDA 监管药物
- 否
- FDA 监管器械
- 否
- 是否有结果
- 否