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出境医 / 临床实验 / A Pilot Biomarker Study Assessing Alpha-synuclein Aggregates Across Biofluid Reservoirs in Patients With Synucleinopathies

A Pilot Biomarker Study Assessing Alpha-synuclein Aggregates Across Biofluid Reservoirs in Patients With Synucleinopathies

Study Description
Brief Summary:
This will be an observational study looking at clinical and biomarker characteristics in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid (CSF) samples will be collected from participants.

Condition or disease Intervention/treatment
Parkinson Disease Multiple System Atrophy Rapid Eye Movement Sleep Behavior Disorder Normal Pressure Hydrocephalus Other: Biomarker assay

Detailed Description:

This is an observational study looking at clinical and biomarker characteristics in patients with Parkinson's disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus (NPH) and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid samples will be collected from participants. Samples will be assessed for levels of misfolded alpha-synuclein aggregates. Clinical characteristics will also be assessed.

Misfolded alpha-synuclein aggregates have the potential to serve as an early biomarker for PD and MSA, increasing the ability to diagnose and treat individuals with these diseases earlier. This study examines the effectiveness of using a novel technique for distinguishing between different parkinsonian disorders by measuring small misfolded α-synuclein aggregates in different biofluids.

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 24 participants
Observational Model: Other
Time Perspective: Other
Official Title: A Pilot Biomarker Study Assessing Alpha-synuclein Aggregates Across Biofluid Reservoirs in Patients With Synucleinopathies
Actual Study Start Date : January 15, 2020
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : June 1, 2022
Arms and Interventions
Group/Cohort Intervention/treatment
Parkinson's Disease
Subjects who have a PD diagnosis
Other: Biomarker assay
Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in biofluid samples from patients with Parkinson's disease, multiple system atrophy, rapid eye movement sleep behavior disorder, normal pressure hydrocephalus and controls.

Multiple System Atrophy
Subjects who have an MSA diagnosis
Other: Biomarker assay
Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in biofluid samples from patients with Parkinson's disease, multiple system atrophy, rapid eye movement sleep behavior disorder, normal pressure hydrocephalus and controls.

Age-matched controls
Subjects who do not have a diagnosed parkinsonian disorder
Other: Biomarker assay
Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in biofluid samples from patients with Parkinson's disease, multiple system atrophy, rapid eye movement sleep behavior disorder, normal pressure hydrocephalus and controls.

Rapid Eye Movement Sleep Behavior Disorder (RBD)
Subjects who have a diagnosis of RBD
Other: Biomarker assay
Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in biofluid samples from patients with Parkinson's disease, multiple system atrophy, rapid eye movement sleep behavior disorder, normal pressure hydrocephalus and controls.

Normal Pressure Hydrocephalus
Subjects who are prescribed a lumbar puncture to treat normal pressure hydrocephalus
Other: Biomarker assay
Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in biofluid samples from patients with Parkinson's disease, multiple system atrophy, rapid eye movement sleep behavior disorder, normal pressure hydrocephalus and controls.

Outcome Measures
Primary Outcome Measures :
  1. Compare levels of misfolded alpha-synuclein aggregates in participants with PD, MSA, RBD, NPH and controls [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein in CSF, serum, plasma, saliva, and urine will be quantified using the protein misfolding cyclic amplification (PMCA) technology


Secondary Outcome Measures :
  1. Investigate the relationship between levels of misfolded alpha-synuclein aggregates and disease severity in PD and MSA [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein aggregates will be quantified using the PMCA technology. PD and MSA disease severity will be assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Unified Multiple System Atrophy Rating Scale (UMSARS), respectively. All groups will receive the MDS-UPDRS III and the RBD Questionnaire.

  2. Investigate the relationship between levels of misfolded alpha-synuclein aggregates across different biofluid reservoirs, including CSF, serum, plasma, saliva, and urine [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein in the different biofluid reservoirs will be quantified using the PMCA technology


Biospecimen Retention:   Samples Without DNA
CSF, plasma, serum, urine

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects with PD, MSA, RBD, NPH and controls
Criteria

For PD subjects:

Inclusion Criteria:

  1. Age 50-75
  2. Diagnosis of idiopathic PD as confirmed by a movement disorder specialist
  3. Age of onset of motor symptoms between 50 - 75
  4. Well-established response to dopaminergic agents and/or amantadine
  5. Ability to complete questionnaires
  6. Ability to provide informed consent
  7. Willingness to go off parkinsonian medication for 12 hours prior to "off" assessment
  8. Medical record includes a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria:

  1. Symptomatic (secondary) parkinsonism (ie. drug induced)
  2. Atypical parkinsonian variants
  3. History of cancer (except basal or squamous cell skin cancer) within 5 years
  4. Known liver disease
  5. Hematological disorders
  6. History of stereotactic or ablative brain surgery
  7. Treatment with an investigational drug or device within the last 30 days
  8. Pregnancy
  9. Inability to comply with or tolerate study procedures
  10. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

MSA Subjects:

Inclusion Criteria:

  1. Age 50-75
  2. Age of onset of motor symptoms between 50-75
  3. Diagnosis of probable or possible MSA as confirmed by a movement disorders specialist
  4. Ability to complete questionnaires
  5. Ability to provide informed consent
  6. Willingness to go off parkinsonian medications for 12 hours prior to "off" assessment
  7. Medical record indicates a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria

  1. Symptomatic (secondary) parkinsonism (ie. drug induced)
  2. History of cancer (except basal or squamous cell skin cancer) within 5 years
  3. Known liver disease
  4. Hematological disorders
  5. History of stereotactic or ablative brain surgery
  6. Treatment with an investigational drug or device within the last 30 days
  7. Pregnancy
  8. Inability to comply with or tolerate study procedures
  9. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For RBD Subjects:

Inclusion Criteria:

  1. Age 50-75
  2. Diagnosis of RBD using current consensus criteria
  3. Ability to provide informed consent
  4. Ability to complete questionnaires
  5. Medical record indicates a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria

  1. Signs for symptoms suggestive of parkinsonian disorder
  2. History of cancer (except basal or squamous cell skin cancer) within 5 years
  3. Known liver disease
  4. Hematological disorders
  5. History of stereotactic or ablative brain surgery
  6. Treatment with an investigational drug or device within the last 30 days
  7. Pregnancy
  8. Inability to comply with or tolerate study procedures
  9. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For NPH:

Inclusion Criteria:

  1. Age 50-75
  2. Scheduled to undergo an LP to evaluate diagnosis of NPH at Stony Brook Neurological Associates
  3. Ability to complete questionnaires
  4. Ability to provide informed consent

Exclusion Criteria:

  1. History of cancer (except basal or squamous cell skin cancer) within 5 years
  2. Known liver disease
  3. Hematological disorders
  4. History of stereotactic or ablative brain surgery
  5. Treatment with an investigational drug or device within the last 30 days
  6. Pregnancy
  7. Inability to comply with or tolerate study procedures
  8. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For Controls:

Inclusion Criteria:

  1. Age 50-75
  2. Scheduled to undergo an LP at Stony Brook Neurological Associates
  3. Ability to complete questionnaires
  4. Ability to provide informed consent

Exclusion Criteria:

  1. Signs or symptoms suggestive of parkinsonian disorder
  2. History of rapid eye movement (REM) Sleep Behavior Disorder (RBD)
  3. History of cancer (except basal or squamous cell skin cancer) within 5 years
  4. Known liver disease
  5. Hematological disorders
  6. History of stereotactic or ablative brain surgery
  7. Treatment with an investigational drug or device within the last 30 days
  8. Pregnancy
  9. Inability to comply with or tolerate study procedures
  10. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Sandra L Skinner, PhD 631-444-7513 sandra.skinner@stonybrookmedicine.edu

Locations
Layout table for location information
United States, New York
Stony Brook University Medical Center Recruiting
Stony Brook, New York, United States, 11794-8121
Contact: Sandra Skinner, PhD    631-444-7513    sandra.skinner@stonybrookmedicine.edu   
Principal Investigator: Carine Maurer, MD,PhD         
Sponsors and Collaborators
Stony Brook University
Investigators
Layout table for investigator information
Principal Investigator: Carine W. Maurer, MD, PhD Stony Brook University Medical Center
Tracking Information
First Submitted Date July 10, 2019
First Posted Date July 15, 2019
Last Update Posted Date March 29, 2021
Actual Study Start Date January 15, 2020
Estimated Primary Completion Date February 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 24, 2021)
Compare levels of misfolded alpha-synuclein aggregates in participants with PD, MSA, RBD, NPH and controls [ Time Frame: 3 weeks ]
Levels of misfolded alpha-synuclein in CSF, serum, plasma, saliva, and urine will be quantified using the protein misfolding cyclic amplification (PMCA) technology
Original Primary Outcome Measures
 (submitted: July 12, 2019)
Compare levels of misfolded alpha-synuclein aggregates in participants with PD, MSA, and controls [ Time Frame: 3 weeks ]
Levels of misfolded alpha-synuclein in CSF, serum, plasma, saliva, and urine will be quantified using the protein misfolding cyclic amplification (PMCA) technology
Change History
Current Secondary Outcome Measures
 (submitted: October 4, 2019)
  • Investigate the relationship between levels of misfolded alpha-synuclein aggregates and disease severity in PD and MSA [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein aggregates will be quantified using the PMCA technology. PD and MSA disease severity will be assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Unified Multiple System Atrophy Rating Scale (UMSARS), respectively. All groups will receive the MDS-UPDRS III and the RBD Questionnaire.
  • Investigate the relationship between levels of misfolded alpha-synuclein aggregates across different biofluid reservoirs, including CSF, serum, plasma, saliva, and urine [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein in the different biofluid reservoirs will be quantified using the PMCA technology
Original Secondary Outcome Measures
 (submitted: July 12, 2019)
  • Investigate the relationship between levels of misfolded alpha-synuclein aggregates and disease severity in PD and MSA [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein aggregates will be quantified using the PMCA technology. PD and MSA disease severity will be assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Unified Multiple System Atrophy Rating Scale (UMSARS), respectively.
  • Investigate the relationship between levels of misfolded alpha-synuclein aggregates across different biofluid reservoirs, including CSF, serum, plasma, saliva, and urine [ Time Frame: 3 weeks ]
    Levels of misfolded alpha-synuclein in the different biofluid reservoirs will be quantified using the PMCA technology
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title A Pilot Biomarker Study Assessing Alpha-synuclein Aggregates Across Biofluid Reservoirs in Patients With Synucleinopathies
Official Title A Pilot Biomarker Study Assessing Alpha-synuclein Aggregates Across Biofluid Reservoirs in Patients With Synucleinopathies
Brief Summary This will be an observational study looking at clinical and biomarker characteristics in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid (CSF) samples will be collected from participants.
Detailed Description

This is an observational study looking at clinical and biomarker characteristics in patients with Parkinson's disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus (NPH) and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid samples will be collected from participants. Samples will be assessed for levels of misfolded alpha-synuclein aggregates. Clinical characteristics will also be assessed.

Misfolded alpha-synuclein aggregates have the potential to serve as an early biomarker for PD and MSA, increasing the ability to diagnose and treat individuals with these diseases earlier. This study examines the effectiveness of using a novel technique for distinguishing between different parkinsonian disorders by measuring small misfolded α-synuclein aggregates in different biofluids.

Study Type Observational
Study Design Observational Model: Other
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
CSF, plasma, serum, urine
Sampling Method Non-Probability Sample
Study Population Subjects with PD, MSA, RBD, NPH and controls
Condition
  • Parkinson Disease
  • Multiple System Atrophy
  • Rapid Eye Movement Sleep Behavior Disorder
  • Normal Pressure Hydrocephalus
Intervention Other: Biomarker assay
Biomarker assay will be used to quantify levels of misfolded alpha-synuclein aggregates in biofluid samples from patients with Parkinson's disease, multiple system atrophy, rapid eye movement sleep behavior disorder, normal pressure hydrocephalus and controls.
Study Groups/Cohorts
  • Parkinson's Disease
    Subjects who have a PD diagnosis
    Intervention: Other: Biomarker assay
  • Multiple System Atrophy
    Subjects who have an MSA diagnosis
    Intervention: Other: Biomarker assay
  • Age-matched controls
    Subjects who do not have a diagnosed parkinsonian disorder
    Intervention: Other: Biomarker assay
  • Rapid Eye Movement Sleep Behavior Disorder (RBD)
    Subjects who have a diagnosis of RBD
    Intervention: Other: Biomarker assay
  • Normal Pressure Hydrocephalus
    Subjects who are prescribed a lumbar puncture to treat normal pressure hydrocephalus
    Intervention: Other: Biomarker assay
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 4, 2019)
24
Original Estimated Enrollment
 (submitted: July 12, 2019)
18
Estimated Study Completion Date June 1, 2022
Estimated Primary Completion Date February 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

For PD subjects:

Inclusion Criteria:

  1. Age 50-75
  2. Diagnosis of idiopathic PD as confirmed by a movement disorder specialist
  3. Age of onset of motor symptoms between 50 - 75
  4. Well-established response to dopaminergic agents and/or amantadine
  5. Ability to complete questionnaires
  6. Ability to provide informed consent
  7. Willingness to go off parkinsonian medication for 12 hours prior to "off" assessment
  8. Medical record includes a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria:

  1. Symptomatic (secondary) parkinsonism (ie. drug induced)
  2. Atypical parkinsonian variants
  3. History of cancer (except basal or squamous cell skin cancer) within 5 years
  4. Known liver disease
  5. Hematological disorders
  6. History of stereotactic or ablative brain surgery
  7. Treatment with an investigational drug or device within the last 30 days
  8. Pregnancy
  9. Inability to comply with or tolerate study procedures
  10. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

MSA Subjects:

Inclusion Criteria:

  1. Age 50-75
  2. Age of onset of motor symptoms between 50-75
  3. Diagnosis of probable or possible MSA as confirmed by a movement disorders specialist
  4. Ability to complete questionnaires
  5. Ability to provide informed consent
  6. Willingness to go off parkinsonian medications for 12 hours prior to "off" assessment
  7. Medical record indicates a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria

  1. Symptomatic (secondary) parkinsonism (ie. drug induced)
  2. History of cancer (except basal or squamous cell skin cancer) within 5 years
  3. Known liver disease
  4. Hematological disorders
  5. History of stereotactic or ablative brain surgery
  6. Treatment with an investigational drug or device within the last 30 days
  7. Pregnancy
  8. Inability to comply with or tolerate study procedures
  9. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For RBD Subjects:

Inclusion Criteria:

  1. Age 50-75
  2. Diagnosis of RBD using current consensus criteria
  3. Ability to provide informed consent
  4. Ability to complete questionnaires
  5. Medical record indicates a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria

  1. Signs for symptoms suggestive of parkinsonian disorder
  2. History of cancer (except basal or squamous cell skin cancer) within 5 years
  3. Known liver disease
  4. Hematological disorders
  5. History of stereotactic or ablative brain surgery
  6. Treatment with an investigational drug or device within the last 30 days
  7. Pregnancy
  8. Inability to comply with or tolerate study procedures
  9. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For NPH:

Inclusion Criteria:

  1. Age 50-75
  2. Scheduled to undergo an LP to evaluate diagnosis of NPH at Stony Brook Neurological Associates
  3. Ability to complete questionnaires
  4. Ability to provide informed consent

Exclusion Criteria:

  1. History of cancer (except basal or squamous cell skin cancer) within 5 years
  2. Known liver disease
  3. Hematological disorders
  4. History of stereotactic or ablative brain surgery
  5. Treatment with an investigational drug or device within the last 30 days
  6. Pregnancy
  7. Inability to comply with or tolerate study procedures
  8. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For Controls:

Inclusion Criteria:

  1. Age 50-75
  2. Scheduled to undergo an LP at Stony Brook Neurological Associates
  3. Ability to complete questionnaires
  4. Ability to provide informed consent

Exclusion Criteria:

  1. Signs or symptoms suggestive of parkinsonian disorder
  2. History of rapid eye movement (REM) Sleep Behavior Disorder (RBD)
  3. History of cancer (except basal or squamous cell skin cancer) within 5 years
  4. Known liver disease
  5. Hematological disorders
  6. History of stereotactic or ablative brain surgery
  7. Treatment with an investigational drug or device within the last 30 days
  8. Pregnancy
  9. Inability to comply with or tolerate study procedures
  10. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)
Sex/Gender
Sexes Eligible for Study: All
Ages 50 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Sandra L Skinner, PhD 631-444-7513 sandra.skinner@stonybrookmedicine.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04020198
Other Study ID Numbers SNCA
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: Identifiers will be removed from participant data or biospecimens. After such removal, the information or biospecimens may be used for future research studies.
Responsible Party Carine Maurer, Stony Brook University
Study Sponsor Stony Brook University
Collaborators Not Provided
Investigators
Principal Investigator: Carine W. Maurer, MD, PhD Stony Brook University Medical Center
PRS Account Stony Brook University
Verification Date March 2021