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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04020198
• Other study ID #: SNCA 1355881
• Status: Active, not recruiting
• Start date: January 15, 2020
• Est. completion date: June 1, 2023

Study information

• Verified date: May 2022
• Source: Stony Brook University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8
• Est. completion date: June 1, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hydrocephalus
• Hydrocephalus, Normal Pressure
• Mental Disorders
• Multiple System Atrophy
• Normal Pressure Hydrocephalus
• Parkinson Disease
• Rapid Eye Movement Sleep Behavior Disorder
• REM Sleep Behavior Disorder
• Shy-Drager Syndrome

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.

Locations

Country	Name	City	State
United States	Stony Brook University Medical Center	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Stony Brook University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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