PD-ENS: Parkinson's Disease Biomarkers in Nerve Cells in the Gut

Sponsor

Weill Medical College of Cornell University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05347407

Collaborator

(none)

Enrollment

Location

25.8

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Parkinson's disease affects all the nerve cells in the body, including the ones in the gut. The gut contains its own nervous system, the enteric nervous system, and can be thought of as a "second brain". This second brain can reflect what is going on in the actual brain. This study is being done to look for biomarkers, or early indicators of developing Parkinson's disease, in the microbiome and in the gut tissue taken during routine screening colonoscopy. People aged 45 and over who are due for their routine screening colonoscopy are eligible to participate.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Procedure: Colonoscopy

Detailed Description

Parkinson's disease affects 1 in 100 people over the age of 65, but the time between disease onset and diagnosis can be many months or years. Interestingly, the pathological hallmarks of Parkinson's disease and other synucleinopathies in the brain can also be seen in the nerve cells in the gut. Parkinson's disease may begin in the gut, at least in some people. Unlike the nerve cells in the brain, the nerve cells in the gut are accessible through routine colonoscopy, and so can be obtained by minimally invasive biopsy for the study in the laboratory. In addition, there are links between gut microbes, including bacteria, and the development of Parkinson's disease.

This research study is being done to discover whether the pathology in enteric nerve cells and the types of bacteria in the gut can serve as an indicator of Parkinson's disease. The goal of this research is to develop a biomarker that could help in earlier diagnosis. It also aims to improve the understanding of the link between the gut and brain in Parkinson's disease.

The American Cancer Society recommends screening colonoscopy starting from the age of 45 for the prevention of colon cancer. The study requires only one visit, and study samples will be collected as part of a colonoscopy needed for routine care.

Study Design

Study Type:

Observational

Anticipated Enrollment :

60 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Biochemical Characterization of Parkinson's Disease-related Proteins in the Enteric Nervous System as a Proxy for Pathological Changes in the Brain

Actual Study Start Date :

Dec 30, 2020

Anticipated Primary Completion Date :

Feb 6, 2023

Anticipated Study Completion Date :

Feb 23, 2023

Arms and Interventions

Arm	Intervention/Treatment
Control Healthy Patients	Procedure: Colonoscopy Patients will be provided with a kit and be asked to bring a stool sample to their colonoscopy appointment. Mucosal biopsies will be collected with standard forceps during colonoscopy. If the physician determines that the patient will need colonoscopy with biopsy as part of their routine clinical care, they will take 6-8 additional biopsies for use in the research study. If the physician determines that the patient will need colonoscopy without biopsy as part of their routine clinical care, they will take 6-8 biopsies for use in the research study only. The collection of additional biopsies will add an estimated two minutes to the whole procedure.
Parkinson's Disease Patients diagnosed with Parkinson's disease	Procedure: Colonoscopy Patients will be provided with a kit and be asked to bring a stool sample to their colonoscopy appointment. Mucosal biopsies will be collected with standard forceps during colonoscopy. If the physician determines that the patient will need colonoscopy with biopsy as part of their routine clinical care, they will take 6-8 additional biopsies for use in the research study. If the physician determines that the patient will need colonoscopy without biopsy as part of their routine clinical care, they will take 6-8 biopsies for use in the research study only. The collection of additional biopsies will add an estimated two minutes to the whole procedure.
At risk for PD Defined as REM sleep behavior disorder, known genetic risk factor, and/or first degree relatives with PD	Procedure: Colonoscopy Patients will be provided with a kit and be asked to bring a stool sample to their colonoscopy appointment. Mucosal biopsies will be collected with standard forceps during colonoscopy. If the physician determines that the patient will need colonoscopy with biopsy as part of their routine clinical care, they will take 6-8 additional biopsies for use in the research study. If the physician determines that the patient will need colonoscopy without biopsy as part of their routine clinical care, they will take 6-8 biopsies for use in the research study only. The collection of additional biopsies will add an estimated two minutes to the whole procedure.
Dementia with Lewy Bodies Patients diagnosed with Dementia with Lewy Body Disease	Procedure: Colonoscopy Patients will be provided with a kit and be asked to bring a stool sample to their colonoscopy appointment. Mucosal biopsies will be collected with standard forceps during colonoscopy. If the physician determines that the patient will need colonoscopy with biopsy as part of their routine clinical care, they will take 6-8 additional biopsies for use in the research study. If the physician determines that the patient will need colonoscopy without biopsy as part of their routine clinical care, they will take 6-8 biopsies for use in the research study only. The collection of additional biopsies will add an estimated two minutes to the whole procedure.
Multiple System Atrophy Patients diagnosed with Multiple System Atrophy	Procedure: Colonoscopy Patients will be provided with a kit and be asked to bring a stool sample to their colonoscopy appointment. Mucosal biopsies will be collected with standard forceps during colonoscopy. If the physician determines that the patient will need colonoscopy with biopsy as part of their routine clinical care, they will take 6-8 additional biopsies for use in the research study. If the physician determines that the patient will need colonoscopy without biopsy as part of their routine clinical care, they will take 6-8 biopsies for use in the research study only. The collection of additional biopsies will add an estimated two minutes to the whole procedure.

Outcome Measures

Primary Outcome Measures

Biochemical changes in enteric nervous system [A single timepoint will be evaluated on biopsy samples taken from subjects during routine screening colonoscopy.]
The primary objective of the study is to assess the abundance and subcellular distribution of alpha-synuclein and other Parkinson's disease-related proteins in the enteric nervous system of PD patients and healthy controls.

Other Outcome Measures

Exploratory Objective [12 months]
Exploratory objectives of the study are to examine whether changes in alpha-synuclein and other biomarkers of Parkinson's disease correlate with age and disease progression. We are interested in whether pathology in the gut precedes or mimics the pathology in the brain, and which areas of the gut are most affected by this pathology. We are also interested in whether we can detect pathological changes in alpha-synuclein and other PD biomarkers, including changes in microbiome, at an early disease stage in humans

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 45-75 years old
Parkinson's Disease defined by the modified UK Parkinson's Disease Society Brain Bank criteria, at risk for the development of Parkinson's disease including REM sleep behavior disorder and/or at least one first degree relative with PD or related disorder, and diseases related to Parkinson's disease including the synucleinopathies Lewy Body Dementia and Multiple System Atrophy.
Baseline Hoehn & Yahr score 1-4
No contraindications to undergoing screening colonoscopy
Able to give informed consent for study participation

Exclusion Criteria:

Clinical features suggestive of a neurodegenerative diagnosis other than synucleinopathy.
Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease, Progressive Supranuclear Palsy (PSP), and Corticobasal syndrome.
Significant concomitant medical disease limiting life expectancy to less than 24 months from study inclusion, or significant and serious concomitant medical disease that is poorly controlled
Signs of active malignant disease or other clinically relevant abnormality on chest x-ray
Active or untreated gastrointestinal disease
Inability to temporarily stop anti-platelet agents or other anti-coagulants without significant risk
Known substance abuse (recent history of abuse of alcohol or other drugs such as barbiturates, cannabinoids and amphetamines) within last 5 years
Contraindication to colonoscopy or associated anesthesia
Pregnancy
In the opinion of the investigator, any other condition regarded as making subject unsuitable for the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medicine	New York	New York	United States	10021

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

Principal Investigator: Jacqueline Burre, PhD, Weill Medical College of Cornell University
Principal Investigator: Virginia M Gao, MD PhD, Weill Medical College of Cornell University