Parkinson's DiseaseNCT04536857
Detection of A-synuclein Aggregate as Biomarker in Diagnosing Parkinson's Disease at Early Stage by Using Protein Misfolding Cyclic Amplification (PMCA)
An observational study of Parkinson's Disease, run by Huashan Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Biomarker assay
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2024to 30 Dec 2025
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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).
Who may be able to join
- 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;
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- 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.
- 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.
- Clinical diagnosis of "probable PSP" by two neurologists specializing in movement disorders according to MDS Clinical Diagnostic Criteria for PSP (2017);
- Age 50-75, disease duration is less than 1 year;
- Metabolic brain network detected by fluorine-18-labelled-fluorodeoxyglucose-PET(18F-FDG PET) is consistent with PSP 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.
- Age 50-75;
- No history of neurodegenerative disease of the central nervous system;
- No history of infective disease of the central system;
- Ability of completing questionnaires;
- Ability of providing informed consent.
Who cannot join
- 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;
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- Inability to comply with study procedures.
- For early MSA patients
- Secondary parkinsonism (ie. drug induced);
- 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 PSP patients
- Secondary parkinsonism (ie. drug induced);
- 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 controls without diagnosis of neurodegenerative disorders
- With prodromal symptoms of PD, such as rapid eye movement sleep behavior disorder (RBD);
- History of being diagnosed as any cancer within 5 years;
- Presence of any condition increasing the risk of the procedure of performing lumbar puncture (LP);
- Pregnancy;
- Inability to comply with study procedures.
Trial locations and contacts
1 site in 1 country.
China1 site
Huashan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200040
About this study
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.
Read the 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.
- Conditions
- Parkinson's Disease
- Being tested
- Biomarker assay
- Keywords
- Parkinson's disease (PD), αSyn aggregates, Protein misfolding cyclic amplification (PMCA), Early diagnosis, CSF
- Medical subject headings
- Parkinson Disease, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biomarker assayOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Parkinson's Disease | Subjects who have a PD diagnosis Receives: Other: Biomarker assay | |
| Multiple System Atrophy | Subjects who have an MSA diagnosis Receives: Other: Biomarker assay | |
| Progressive Superanuclear Palsy | Subjects who have a PSP diagnosis Receives: Other: Biomarker assay | |
| Age-matched controls | Subjects who do not have a diagnosed neurological disorder Receives: Other: Biomarker assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: two years
Secondary outcomes (8)
The correlation between the PMCA T50 and MDS-UPDRS III score at baseline in PD patients
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).
Measured: two years
The correlation between PMCA T50 and subregional DAT in striatum in PD patients
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.
Measured: two years
The correlation between PMCA T50 and PDRP expression value in PD patients
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.
Measured: two years
The correlation between PMCA T50 and the change of MDS-UPDRS III score between the baseline and the follow-up
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.
Measured: two years
The sensitivity
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).
Measured: two years
The specificity
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).
Measured: two years
The positive predictive value
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).
Measured: two years
The negative predictive value
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).
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start1 Oct 2024 (estimated)
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Why it stopped: Our applied project did not receive funding support, so it cannot proceed, leading to the withdrawal of the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Huashan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Wang, Huashan Hospital
- Investigators
- Jian Wang, MD, Principal investigator, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04536857
- Sponsor's protocol ID
- 2020 Provisional Audit No.1004
- Status last verified
- Mar 2025
- First submitted
- 28 Aug 2020
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection of A-synuclein Aggregate as Biomarker in Diagnosing Parkinson's Disease at Early Stage by Using Protein Misfolding Cyclic Amplification (PMCA)
- ClinicalTrials.gov ID
- NCT04536857
- Acronym / sponsor ID
- 2020 Provisional Audit No.1004
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease (PD), αSyn aggregates, Protein misfolding cyclic amplification (PMCA), Early diagnosis, CSF
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Our applied project did not receive funding support, so it cannot proceed, leading to the withdrawal of the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 3 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Parkinson's Disease | – | Other: Biomarker assaySubjects who have a PD diagnosis |
| Multiple System Atrophy | – | Other: Biomarker assaySubjects who have an MSA diagnosis |
| Progressive Superanuclear Palsy | – | Other: Biomarker assaySubjects who have a PSP diagnosis |
| Age-matched controls | – | Other: Biomarker assaySubjects who do not have a diagnosed neurological disorder |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (25 listed)
- 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;
Key exclusion criteria (25 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biomarker assayBiomarker 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. | Other | Age-matched controls, Multiple System Atrophy, Parkinson's Disease, Progressive Superanuclear Palsy |
Primary outcome
The area under curve of the PMCA for the early diagnosis of PD
Time frame: 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.
8 secondary outcomes
The correlation between the PMCA T50 and MDS-UPDRS III score at baseline in PD patients
Time frame: two years
The correlation between PMCA T50 and subregional DAT in striatum in PD patients
Time frame: two years
The correlation between PMCA T50 and PDRP expression value in PD patients
Time frame: two years
The correlation between PMCA T50 and the change of MDS-UPDRS III score between the baseline and the follow-up
Time frame: two years
The sensitivity
Time frame: two years
The specificity
Time frame: two years
The positive predictive value
Time frame: two years
The negative predictive value
Time frame: two years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jian Wang, MD principal investigator
Huashan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson's Disease, run by Huashan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The area under curve of the PMCA for the early diagnosis of PD (time frame: two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.