Detection of A-synuclein Aggregate As Biomarker in Diagnosing Parkinson's Disease At Early Stage by Using Protein Misfolding Cyclic Amplification (PMCA)
- Conditions
- Parkinson's Disease
- Interventions
- Other: Biomarker assay
- Registration Number
- NCT04536857
- Lead Sponsor
- Huashan Hospital
- Brief Summary
The study will investigate the biomarker of a-synuclein aggregate in CSF detected by protein misfolding cyclic amplification (PMCA) and its sensitivity and specificity in diagnosing Parkinson's disease at H-Y stage I and disease duration less than 1 year, compared with that from age-matched controls without neurodegeneration, those with Multiple System Atrophy (MSA) as a disease control with a-synucleinopathy, and those with Progressive Supranuclear Palsy (PSP) as a control with non-a-synucleinopathy neurodegeneration.
- Detailed Description
This will be an observational study aiming to develop the protein misfolding cyclic amplification (PMCA) technology that detects minute amounts of αSyn aggregates circulating in cerebrospinal fluid (CSF) as a novel assay with high sensitivity and specificity for the early diagnosis of PD. To achieve this goal, we will apply the PMCA to detect the αSyn aggregates in the CSF samples acquired from a discovery cohort that consist of well-characterized early PD patients (disease duration ≤1 year and Hoehn and Yahr Stage I, and DAT-PET and FDG-PET meet the imaging features of PD, n=75) and gender, age-matched healthy controls (n=38). Furthermore, we will confirm the findings in a separate confirmatory cohort with well-characterized early PD patients (disease duration ≤1 year and Hoehn and Yahr Stage I, and DAT-PET and FDG-PET meet the imaging features of PD, n=75), early multiple system atrophy (MSA) patients (disease duration ≤1 year, n=38), early progressive supranuclear palsy (PSP) patients (disease duration ≤1 year, n=38) and age-matched healthy controls (n=38). The sensitivity, specificity, positive predictive value, negative predictive value, and area under curve of the PMCA for the early diagnosis of PD will be calculated in the discovery cohort and be confirmed in the confirmatory cohort, respectively. In addition, the clinical characteristics, including motor and nonmotor symptoms of early PD, MSA and PSP patients in the two cohort will be comprehensively assessed at baseline and during followed-up. To assess the value of the PMCA technology in the evaluation of the disease severity and progress, we will perform the partial correlation analysis between clinical features of early PD patients and the PMCA T50 defined as the time needed to reach 50% of the maximum aggregation.
Misfolded αSyn aggregates have the potential to serve as a biomarker for early PD. The PMCA technology could detect small quantities of misfolded αSyn aggregates by taking advantage of their ability to nucleate further aggregation, enabling a very high amplification of the signal. This study examines the effectiveness of using the PMCA as a novel technique for discriminating early PD from gender, age-matched healthy controls and other early parkinsonian disorders (MSA, PSP) by detecting small misfolded αSyn aggregates in CSF.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 302
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Parkinson's Disease Biomarker assay Subjects who have a PD diagnosis Multiple System Atrophy Biomarker assay Subjects who have an MSA diagnosis Progressive Superanuclear Palsy Biomarker assay Subjects who have a PSP diagnosis Age-matched controls Biomarker assay Subjects who do not have a diagnosed neurological disorder
- Primary Outcome Measures
Name Time Method The area under curve of the PMCA for the early diagnosis of PD two years The area under curve is used to show the ability of the a-syn-PMCA to diagnose early PD. The value of area under curve is higher, then the ability of the a-syn-PMCA to diagnose early PD is stronger.
- Secondary Outcome Measures
Name Time Method The correlation between PMCA T50 and the change of MDS-UPDRS III score between the baseline and the follow-up two years PMCA T50 is the time needed to reach 50% of the maximum aggregation. The change of MDS-UPDRS III score is the difference of that between the baseline and the follow-up.
The negative predictive value two years The negative predictive value is used to show the ability of the a-syn-PMCA to correctly label people who test negative, and is represented by true negative / (false negative + true negative).
The specificity two years The specificity is used to show the ability of the a-syn-PMCA to avoid false early PD patients and rule out early PD patients, and is represented by true negative/ (false positive + true negative).
The correlation between PMCA T50 and subregional DAT in striatum in PD patients two years PMCA T50 is the time needed to reach 50% of the maximum aggregation. The DAT uptake value (caudate, anterior putamen and/or posterior putamen) will be quantified using DAT-PET.
The correlation between the PMCA T50 and MDS-UPDRS III score at baseline in PD patients two years PMCA T50 is the time needed to reach 50% of the maximum aggregation. The motor symptoms of PD patients will be assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS- III).
The correlation between PMCA T50 and PDRP expression value in PD patients two years PMCA T50 is the time needed to reach 50% of the maximum aggregation. The Parkinson's disease-related pattern (PDRP) expression value will be quantified by using FDG-PET.
The sensitivity two years The sensitivity is used to show the ability of the a-syn-PMCA to diagnose early PD patients, and is represented by true positive/ (true positive +false negative).
The positive predictive value two years The positive predictive value is used to show the ability of the a-syn-PMCA to correctly label early PD patients who test positive, and is represented by true positive / (true positive + false positive).
Trial Locations
- Locations (1)
Huashan Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China