Parkinson DiseaseNCT07026929
Neuro-immune Interactome in Parkinson's Disease
An observational study of Parkinson Disease, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- 10 May 2021to Jun 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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).
Show all 13Show fewer
- 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.
Who cannot join
- 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).
Show all 22Show fewer
- 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.
- Additional Exclusion Criteria for Subjects with diagnosis of PD:
- Meets any of the MDS exclusionary criteria for PD diagnosis. Additional Exclusion Criteria for Subjects with RBD
- An identified secondary cause of RBD.
- Neurodegenerative Disease: Neurological examination must be performed to exclude parkinsonism (according to MDS PD criteria), and clinically evident dementia.
- Secondary RBD, caused by antidepressant medications (antidepressant- triggered RBD can be included provided that diagnosis is documented of antidepressant medications, and patients can be taking antidepressants during the study).
- Diagnosis of narcolepsy. Additional Exclusion Criteria for Healthy Control Subjects
- History of Parkinson's disease in a first-degree blood relative.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06520
About this study
Official title: Tracing the Origin and Progression of Parkinson's Disease Through the Neuro-Immune Interactome
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.
Read the detailed description
The primary objective of this study is to determine whether T cell-mediated autoimmunity initiates the neurodegenerative process in PD, and if these early immunological processes converge on classic archetypes of neurodegeneration.
Secondary objectives of this study are to determine to what extent the T cell-mediated autoimmune process initiates in the gut microbiome; and whether or not different PD- related genes or HLA type are associated with the presence of T cell-mediated autoimmunity.
Investigators hypothesize that progression of Parkinson's Disease (PD) pathology is initiated and/or abetted by an autoimmune process involving alpha-synuclein-specific T cell activation triggered by gut microbiome dysbiosis, followed by neuro-immune interactions that establish PD in the brain. Investigators propose to address this hypothesis by integrating neuroimmunology, single cell genomics, mouse models, and microbiome approaches.
- Conditions
- Parkinson Disease
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterization of of T cells
Number and types of T cells which autoreact to alpha- synuclein in the blood and cerebral spinal fluid (CSF)
Measured: 2 months
Secondary outcomes (2)
Presence of increased clonality of T cells
The presence of increased clonality of T cells reflecting increased immune cell activation will be assessed in Mononuclear cells (PBMCs) and nucleated cells in the CSF isolated and prepared for single cell RNA sequencing.
Measured: 2 months
presence of cross reactivity of anti-alpha- synuclein T cells
Presence of cross reactivity of anti-alpha- synuclein T cells with microbial agents from subject gut stool samples using cells isolated and prepared for single cell RNA sequencing.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2025
- Study start10 May 2021
- Primary completion27 Jun 2024
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Sponsor
- Investigators
- Jesse Cedarbaum, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07026929
- Sponsor's protocol ID
- 2000029032
- Status last verified
- Jul 2026
- First submitted
- 10 Jun 2025
- Last updated
- 21 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All deidentified data not considered PHI and permitted to be released per participants' consent will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tracing the Origin and Progression of Parkinson's Disease Through the Neuro-Immune Interactome
- ClinicalTrials.gov ID
- NCT07026929
- Acronym / sponsor ID
- 2000029032
- Conditions
- Parkinson Disease
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- 10 May 2021 (actual)
- Primary completion
- 27 Jun 2024 (actual)
- Study completion
- Jun 2031 (estimated)
- First posted
- 18 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objective of this study is to determine whether T cell-mediated autoimmunity initiates the neurodegenerative process in PD, and if these early immunological processes converge on classic archetypes of neurodegeneration.
Secondary objectives of this study are to determine to what extent the T cell-mediated autoimmune process initiates in the gut microbiome; and whether or not different PD- related genes or HLA type are associated with the presence of T cell-mediated autoimmunity.
Investigators hypothesize that progression of Parkinson's Disease (PD) pathology is initiated and/or abetted by an autoimmune process involving alpha-synuclein-specific T cell activation triggered by gut microbiome dysbiosis, followed by neuro-immune interactions that establish PD in the brain. Investigators propose to address this hypothesis by integrating neuroimmunology, single cell genomics, mouse models, and microbiome approaches.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (13 listed)
- English Speaking
- Able and willing to provide informed consent
- 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.
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Characterization of of T cells
Time frame: 2 months
Number and types of T cells which autoreact to alpha- synuclein in the blood and cerebral spinal fluid (CSF)
2 secondary outcomes
Presence of increased clonality of T cells
Time frame: 2 months
presence of cross reactivity of anti-alpha- synuclein T cells
Time frame: 2 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: Yes. All deidentified data not considered PHI and permitted to be released per participants' consent will be made available.
Related trials for Parkinson Disease
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
RecruitingPhase 3
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Cervical Cancer
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesse Cedarbaum principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of of T cells (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.