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

Terminated

• Conditions: Rapid Eye Movement Sleep Behavior Disorder; Normal Pressure Hydrocephalus; Parkinson Disease; Multiple System Atrophy
• Interventions: Other: Biomarker assay

• Registration Number: NCT04020198
• Lead Sponsor: Stony Brook University

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 Timeline

• Study First Submitted: 2019-07-10
• Study First Submitted QC: 2019-07-12
• Study First Posted: 2019-07-15
• Study Start: 2020-01-15
• Primary Completion: 2022-10-19
• Study Completion: 2022-10-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Rapid Eye Movement Sleep Behavior Disorder (RBD)	Biomarker assay	Subjects who have a diagnosis of RBD
Multiple System Atrophy	Biomarker assay	Subjects who have an MSA diagnosis
Parkinson's Disease	Biomarker assay	Subjects who have a PD diagnosis
Age-matched controls	Biomarker assay	Subjects who do not have a diagnosed parkinsonian disorder
Normal Pressure Hydrocephalus	Biomarker assay	Subjects who are prescribed a lumbar puncture to treat normal pressure hydrocephalus

Primary Outcome Measures

Name	Time	Method
Compare levels of misfolded alpha-synuclein aggregates in participants with PD, MSA, RBD, NPH and controls	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

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

Trial Locations

Locations (1)

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States