- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04239079
Autoimmune Features of Neurodegenerative Disorders
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 1) 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.
Study Overview
Status
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Kim Tran
- Phone Number: (646)774-5023
- Email: nkt2118@cumc.columbia.edu
Study Locations
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New York
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New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center
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Contact:
- Kim Tran
- Phone Number: 646-774-5023
- Email: nkt2118@cumc.columbia.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
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PD and Controls
50% of the participants will be healthy controls and 50% will be patients diagnosed with Parkinson's disease
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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)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of subjects with T-cell immune response
Time Frame: Week 1-2
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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.
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Week 1-2
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Karen Marder, MD, MPH, Columbia University
- Principal Investigator: David Sulzer, PhD, Columbia University
- Principal Investigator: Chih-Chun Lin, MD, PhD, Columbia University
Publications and helpful links
General Publications
- Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A. T cells from patients with Parkinson's disease recognize alpha-synuclein peptides. Nature. 2017 Jun 29;546(7660):656-661. doi: 10.1038/nature22815. Epub 2017 Jun 21. Erratum In: Nature. 2017 Sep 13;549(7671):292.
- Garretti F, Agalliu D, Lindestam Arlehamn CS, Sette A, Sulzer D. Autoimmunity in Parkinson's Disease: The Role of alpha-Synuclein-Specific T Cells. Front Immunol. 2019 Feb 25;10:303. doi: 10.3389/fimmu.2019.00303. eCollection 2019.
- Lindestam Arlehamn CS, Garretti F, Sulzer D, Sette A. Roles for the adaptive immune system in Parkinson's and Alzheimer's diseases. Curr Opin Immunol. 2019 Aug;59:115-120. doi: 10.1016/j.coi.2019.07.004. Epub 2019 Aug 17.
- Lindestam Arlehamn CS, Pham J, Alcalay RN, Frazier A, Shorr E, Carpenter C, Sidney J, Dhanwani R, Agin-Liebes J, Garretti F, Amara AW, Standaert DG, Phillips EJ, Mallal SA, Peters B, Sulzer D, Sette A. Widespread Tau-Specific CD4 T Cell Reactivity in the General Population. J Immunol. 2019 Jul 1;203(1):84-92. doi: 10.4049/jimmunol.1801506. Epub 2019 May 13.
- Lindestam Arlehamn CS, Dhanwani R, Pham J, Kuan R, Frazier A, Rezende Dutra J, Phillips E, Mallal S, Roederer M, Marder KS, Amara AW, Standaert DG, Goldman JG, Litvan I, Peters B, Sulzer D, Sette A. alpha-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease. Nat Commun. 2020 Apr 20;11(1):1875. doi: 10.1038/s41467-020-15626-w.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Dementia
- Tauopathies
- Cognition Disorders
- Parkinson Disease
- Alzheimer Disease
- Cognitive Dysfunction
- Neurodegenerative Diseases
Other Study ID Numbers
- AAAS1669
- 1R01NS095 435-01A1 (Other Grant/Funding Number: National Institute of Neurological Disorders and Stroke)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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