Detection of A-synuclein Aggregate as Biomarker in Diagnosing Parkinson's Disease at Early Stage by Using Protein Misfolding Cyclic Amplification (PMCA)

NCT04536857 | Withdrawn DMC

• 1 other identifier: 2020 Provisional Audit No.1004
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease (PD); αSyn aggregates; Protein misfolding cyclic amplification (PMCA); Early diagnosis; CSF

Outcome Measures

Primary Outcomes (1)

• The area under curve of the PMCA for the early diagnosis of PD

  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.

  two years

Secondary Outcomes (8)

• The correlation between the PMCA T50 and MDS-UPDRS III score at baseline in PD patients

  two years

• The correlation between PMCA T50 and subregional DAT in striatum in PD patients

  two years

• The correlation between PMCA T50 and PDRP expression value in PD patients

  two years

• The correlation between PMCA T50 and the change of MDS-UPDRS III score between the baseline and the follow-up

  two years

• The sensitivity

  two years

Study Arms (4)

Parkinson's Disease

Subjects who have a PD diagnosis

Other: Biomarker assay

Multiple System Atrophy

Subjects who have an MSA diagnosis

Other: Biomarker assay

Progressive Superanuclear Palsy

Subjects who have a PSP diagnosis

Other: Biomarker assay

Age-matched controls

Subjects who do not have a diagnosed neurological disorder

Other: Biomarker assay

Interventions

Biomarker assay OTHER

Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in cerebrospinal fluid from patients with Parkinson's disease, multiple system atrophy, progressive superanuclear palsy and controls.

Age-matched controls; Multiple System Atrophy; Parkinson's Disease; Progressive Superanuclear Palsy

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Discovery cohort: (1) Early PD patients (disease duration ≤1 year and Hoehn and Yahr Stage I, n=75); (2) Gender, age-matched healthy controls (n=38); (3) The dopamine reuptake transporter (DAT) is significantly reduced in striatum on PET imaging; (4) Metabolic brain network detected by fluorine-18-labelled-fluorodeoxyglucose-PET(18F-FDG PET) is consistent with Parkinson's disease-related pattern (PDRP). Confirmatory cohort: (1) Early PD patients (disease duration ≤1 year and Hoehn and Yahr Stage I, n=75); (2) Early Multiple System Atrophy (MSA) patients (disease duration ≤1 year, n=38); (3) Early progressive supranuclear palsy (PSP) patients (disease duration ≤1 year, n=38); (4) Gender, age-matched healthy controls (n=38); (5) The dopamine reuptake transporter (DAT) is significantly reduced in striatum on PET imaging; (6) Metabolic brain network detected by fluorine-18-labelled-fluorodeoxyglucose-PET(18F-FDG PET) is consistent with Parkinson's disease-related pattern (PDRP).

You may qualify if:

• Clinical diagnosis of "probable PD" by two neurologists specializing in movement disorders according to the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for PD (2015);
• Age 50-75, disease duration is less than 1 year, and Hoehn \& Yahr Stage I;
• the dopamine reuptake transporter (DAT) is significantly reduced in striatum on PET imaging;
• Metabolic brain network detected by fluorine-18-labelled-fluorodeoxyglucose-PET(18F-FDG PET) is consistent with Parkinson's disease-related pattern (PDRP), with FDG hypermetabolism being in basal ganglia and cerebellum;
• Good response to anti-PD medications;
• Ability of completing questionnaires;
• Ability of providing informed consent;
• Willingness of being assessed by neurologists during off-medication state defined as discontinuing anti-PD medications for at least 12 hours before assessment.

You may not qualify if:

• Secondary parkinsonism (ie. drug induced);
• Atypical parkinsonisms like MSA or PSP etc;
• Presence of any item in 10 red flags of the MDS Clinical Diagnostic Criteria for PD (2015) in the comprehensive assessments during follow-up;
• History of being diagnosed as any cancer within 5 years;
• Presence of any condition risking the procedure of performing lumbar puncture (LP);
• Pregnancy;
• Inability to comply with study procedures.
• For early MSA patients
• Clinical diagnosis of "probable MSA" by two neurologists specializing in movement disorders according to the International Parkinson and Movement Disorder Society (MDS) second consensus criteria for MSA (2019);
• Age 50-75, and disease duration is less than 1 year;
• Metabolic brain network detected by fluorine-18-labelled-fluorodeoxyglucose-PET(18F-FDG PET) is consistent with MSA related pattern;
• Ability of completing questionnaires;
• Ability of providing informed consent;
• Willingness of being assessed by neurologists during off-medication state defined as discontinuing anti-PD medications for at least 12 hours before assessment.
• Secondary parkinsonism (ie. drug induced);

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

cerebrospinal fluid

MeSH Terms

Conditions

Parkinson Disease; Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jian Wang, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Deputy Director, Department of Neurology

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 3, 2020
• Study Start: October 1, 2024
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: March 19, 2025

Record last verified: 2025-03

Locations

CN (1)