Autoimmune Features of Neurodegenerative Disorders

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04239079

Collaborator

(none)

120

Enrollment

Location

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being conducted to better understand the role of inflammation in Parkinson's disease (PD) and Alzheimer's disease (AD). The investigators plan to recruit 30 PD, 30 AD/Amnestic Mild Cognitive Impairment (aMCI), and 60 age matched healthy controls in this study to study the role of immune response in PD and AD.

The study involves up to two study visits involving brief questionnaires and blood draw of up to 250cc (approximately 17 tablespoons) to be collected. More ways to participate, including

smaller amount blood donation (up to 100cc per visit for 1-2 visits); and 2) participation via tele-visit and mobile phlebotomy visits (blood donation up to 50cc, ~5 tubes, by a certified mobile phlebotomist at home/location of choice) now available.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease Alzheimer Disease Mild Cognitive Impairment

Detailed Description

Neurodegenerative diseases are characterized by the misprocessing of specific proteins, but how and if this results in cell death is unknown. This study is being conducted to better understand the role of inflammation in Parkinson's disease (PD) and Alzheimer's disease (AD). Both AD and PD have long been known to feature prominent neuroinflammatory components. Preliminary studies have found autoimmune features in several patients including recognition of self-antigens by specific T cells. This study will test the hypothesis that AD and PD are associated with self-derived antigens (alpha-syn and tau protein) that become recognized by T cells during aging and disease. The overall aim is to identify antigenic responses associated with PD and AD. The specific aims include:

Identify the protein(s) or protein segments that may trigger inflammation
Identify the T cells (immune cells) that may recognize and kill brain cells (neurons and astrocytes)
Identify the genetic profile associated with this immune response (genetic analysis of the immune system)

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Autoimmune Features of Neurodegenerative Disorders

Actual Study Start Date :

May 1, 2019

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
PD and Controls 50% of the participants will be healthy controls and 50% will be patients diagnosed with Parkinson's disease
AD/aMCI and Controls 50% of the participants will be healthy controls and 50% will be patients diagnosed with Alzheimer's disease or Amnestic Mild Cognitive Impairment (aMCI)

Outcome Measures

Primary Outcome Measures

Percentage of subjects with T-cell immune response [Week 1-2]
Blood samples from patients and controls will be processed. The presence of T cell response against the candidate antigens by patient blood-derived peripheral blood mononuclear cells (PBMC) will be assessed using an enzyme-linked immunosorbent spot (ELISPOT) assay.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

PD and age matched controls:

For PD participants (n=30):

Inclusion criteria:

Clinical diagnosed PD based on UK Brain Bank criteria for the clinical diagnosis of PD. And must demonstrate two of the following three, as modified from BioFIND criteria: rest tremor, rigidity, or bradykinesia, with dopaminergic medication benefit
Age at recruitment ≥ 55
Age at motor onset > 45
PD onset age between 50-75 years
Willingness to have genotyping and genetic studies

Exclusion criteria:

Atypical features indicative of a Parkinson-Plus disorder (Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD)) including cerebellar signs, supranuclear gaze palsy, apraxia and other cortical signs, or prominent autonomic failure, neuroleptic treatment at time of onset of parkinsonism, active treatment with a neuroleptic at time of study entry, history of repeated strokes with stepwise progression of parkinsonism, history of repeated head injury, history of definite encephalitis, prominent gait imbalance early in the course (< 5 years)
History of Dementia
Recent history of cancer (past 3 years), except skin cancer
Autoimmune disease
Disease of the immune system (e.g. chronic leukemia, HIV)
On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
Inability to provide informed consent.

For age-matched control participants (n=30):

Inclusion criteria:

Ages ≥55 years old
With lack of PD in first-degree blood relatives
Montreal Cognitive Assessment (MoCA): ≥26
Willingness to have genotyping and genetic studies

Exclusion criteria:

Recent history of cancer (past 3 years), except skin cancer
Autoimmune disease
Disease of the immune system (e.g. chronic leukemia, HIV)
On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
Inability to provide informed consent

AD/aMCI and age matched controls:

For AD/aMCI participants (n=30):

Inclusion criteria:

Clinically diagnosed mild AD/amnestic MCI. The severity will be accessed through the Clinical Dementia Rating Scale (CDR). CDR equal to 0.5 or 1 will be necessary to meet criteria. Participants with advanced AD stage will not be capable to give their consent.
Age ≥55 years old
Mini-Mental State Exam (MMSE): 20-26
Willingness to have genotyping and genetic studies

Exclusion criteria:

Other forms of dementia including frontotemporal dementia or other dementia associated with parkinsonism such as Dementia with Lewy bodies (DLB), or Parkinson's disease Dementia (PDD), Progressive Supranuclear Palsy or corticobasal degeneration.
History of Parkinson's disease (PD)
Recent history of cancer (past 3 years), except skin cancer
Autoimmune disease
Disease of the immune system (e.g. chronic leukemia, HIV)
On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
Inability to provide informed consent

For age-matched control participants (n=30):

Inclusion criteria:

Healthy volunteers ≥55 years old
CDR: 0
MoCA: ≥26
Willingness to have genotyping and genetic studies

Exclusion criteria:

History of Parkinson's disease (PD)
Recent history of cancer (past 3 years), except skin cancer
Autoimmune disease
Disease of the immune system (e.g. chronic leukemia, HIV)
On chronic immune-modulatory therapy (e.g. oral steroids, azathioprine, rituximab)
Inability to provide informed consent