Neuro-immune Interactome in Parkinson's Disease

NCT07026929 | Active Not Recruiting

• 1 other identifier: 2000029032
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be observational and have a prospective case-control longitudinal design. Eligible subjects with idiopathic REM behavior disorder (RBD), Parkinson's disease with RBD, and healthy controls will be recruited. Subjects will undergo a sleep study to determine eligibility for the study and then in the study will undergo clinical assessments, including cognitive, sensory and motor clinical assessment, dopamine transporter scanning, and smell testing. Eligible subjects will undergo phlebotomy, lumbar puncture, stool and saliva collection, and genome-wide association scans at baseline and then undergo yearly sensory and motor clinical assessment to assess for phenoconversion to neurodegenerative disease. From blood and CSF samples, investigators will isolate mononuclear cells, and using cell immunologic and single cell genomic procedures, will look for the presence of T cells which autoreact with alpha-synuclein. Investigators will also look for the presence of increased clonality of T cells reflecting increased immune cell activation and the presence of cross reactivity of anti-alpha-synuclein T cells with microbial agents from subject gut stool samples.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Characterization of of T cells

  Number and types of T cells which autoreact to alpha- synuclein in the blood and cerebral spinal fluid (CSF)

  2 months

Secondary Outcomes (2)

• Presence of increased clonality of T cells

  2 months

• presence of cross reactivity of anti-alpha- synuclein T cells

  2 months

Study Arms (5)

RBD without motor or cognitive dysfunction

Participants with RBD without motor or cognitive dysfunction, normal DaT Scan, no complaints of constipation, normosmic (at no or remote risk for PD)

RBD and asymmetric

Participants with RBD and asymmetric, reduced signal on DaT scan, symptomatic constipation, or hyposmia with or without minor motor signs of PD (at-risk for PD)

RBD with PD

Participants with RBD and PD for less than 10 years (10 years from PD diagnosis at the time subject was first identified to be screened for the study)

PD without RBD

Participants with PD without RBD

Healthy controls

no RBD, no PD

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from outpatient neurology and sleep medicine clinics and from the community using flyers and social media postings. Subjects in general will be healthy adults seen in an outpatient research setting. There will be no limitation in ability to move or walk as most subjects will be pre-clinical except for Group 4 which will include persons with only minor motor symptoms (which never includes gait disturbance) of PD.

You may qualify if:

• General:
• English Speaking
• Able and willing to provide informed consent
• REM behavior disorder:
• Repeated episodes of sleep-related vocalization and/or complex motor behaviors. These behaviors are documented by polysomnography to occur during REM sleep or, based on clinical history of dream enactment, are presumed to occur during REM sleep.
• Polysomnographic recording demonstrates REM sleep without atonia (RWA).
• The disturbance is not better explained by another sleep disorder, mental disorder, medication, or substance abuse.
• Parkinson's disease:
• Meets the Movement Disorders Society criteria for Clinically Probable Parkinson's disease.
• Disease duration \< 10 years 10 years from PD diagnosis at the time subject was first identified to be screened for the study.
• Healthy controls:
• No clinical evidence of Parkinson's disease or RBD.
• Normosmic.

You may not qualify if:

• General:
• Known immune deficiency disorder.
• Personal history of any neurological disorder, including but not limited to:
• Multiple Sclerosis, Alzheimer's disease, Multiple System Atrophy, Progressive Supranuclear Palsy, Amyotrophic Lateral Sclerosis, or repeated head trauma.
• Solid or hematological malignancy other than in-situ carcinoma of the cervix or basal cell carcinoma of the skin unless the subject has no evidence of active disease and has not received treatment, including chemotherapy, immunotherapy or radiation treatment within previous 12 months.
• Known blood clotting disorder (with increased likelihood of bleeding).
• Short Bowel Syndrome, Ileostomy, or colostomy
• History of vagotomy.
• Taking anticoagulant or antiplatet medication (coumadin, heparin, apixaban (Eliquis ®), rivaroxaban (Xalreto®), edoxaban (Lixiana®), or dabigatran (Praxeda®). Low-dose (100 mg/day or less) aspirin is allowed. Taking certain drugs that can interfere with interpretation of DaT scan, such as methylphenidate (Ritalin®), stimulant drugs such as phentermine or ephedrine, certain antidepressants, including mazindol, or radaraxine, benztropine (Cogentin®) within 5 half-lives prior to the date of the scheduled DaT scan. Subjects taking a potentially interfering medication can only be included if the medication is stopped with the concurrence of the subject and the prescribing health care provider. Persons taking bupropion or amphetamine will be asked to hold the medicine on the morning of the scan. They will be able to take the medicine the same day after the scan. Inability to hold bupropion or an amphetamine for the scan, however, will not exclude an individual from participating.
• Receiving chemotherapy agents with ability to affect the immune system, or radiation therapy (within the past 12 months).
• Receiving potent immunosuppressant agents (e.g., anti-TNF, or IL-6 antibodies, JAK/STAT inhibitors, chemotherapy agents such as methotrexate or Cytoxan used to induce immunosuppression), Use of low, maintenance doses of corticosteroids may be permitted, depending on the underlying disease indication.
• Treatment with an experimental agent within 3 months of screening.
• Pregnancy or actively breast feeding.
• Treatment of thyroid disease with radioactive iodine.
• Lidocaine allergy.

Sponsors & Collaborators

• Yale University: lead
• Fox (Michael J.) Foundation for Parkinson's Research: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Jesse Cedarbaum

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start: May 10, 2021
• Primary Completion: June 27, 2024
• Study Completion (Estimated): June 1, 2031
• Last Updated: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: At the time of publication of the primary manuscript
• Access Criteria: Public

Locations

US (1)