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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease; Multiple System Atrophy; Normal Pressure Hydrocephalus; Rapid Eye Movement Sleep Behavior Disorder
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794-8121
      • Stony Brook University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with PD, MSA, RBD, NPH and controls

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

Number of groups / cohorts

5

Cohorts 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the relationship between levels of misfolded alpha-synuclein aggregates and disease severity in PD and MSA	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.	3 weeks
Investigate the relationship between levels of misfolded alpha-synuclein aggregates across different biofluid reservoirs, including CSF, serum, plasma, saliva, and urine	Levels of misfolded alpha-synuclein in the different biofluid reservoirs will be quantified using the PMCA technology	3 weeks

Collaborators and Investigators

• Sponsor: Stony Brook University
• Investigators: Principal Investigator: Carine W. Maurer, MD, PhD, Stony Brook University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (Actual): July 15, 2019

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Alpha-synuclein
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Parasomnias; Proteostasis Deficiencies; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; REM Sleep Parasomnias; Parkinson Disease; Mental Disorders; Multiple System Atrophy; Shy-Drager Syndrome; Synucleinopathies; REM Sleep Behavior Disorder; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: SNCA 1355881

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No