SudoScan as a Biomarker of Parkinson's Disease

Currently, there is no clear diagnostic test that can be used to confirm the diagnosis of Parkinson's disease, or a biomarker that can track its progression. Patients with Parkinson's have many abnormalities of the autonomic nervous system, which may be related to Parkinson's changes outside of the brain. A new device called the SudoScan, which measures autonomic sweating changes, may be a simple way to test for autonomic changes in Parkinson's.

The investigator plan to see whether SudoScan can identify Parkinson's disease and whether SudoScan abnormalities might be present even in early (prodromal) Parkinson's stages.

The investigator will assess SudoScan in a group of Parkinson's patients, normal healthy controls, patients with non-Parkinson's neurodegeneration, and patients with REM sleep behavior disorder (an early/prodromal Parkinson's state). Abnormalities will be correlated with standard autonomic tests and with skin biopsy findings Parkinson's degeneration in the peripheral autonomic fibers.

If the investigator can find a reliable way to diagnose and follow Parkinson's disease, he will be able to correctly identify Parkinson's (even in its earliest stages). This will improve the chance to find protective treatments against Parkinson's, by preventing false diagnosis and by providing a new marker to track disease progression.

If successful, the investigator will aim to validate the findings on a large sample of Parkinson's and also to track changes over time in the original cohorts

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Device: Sudoscan and clinical assessment; Genetic: Skin biopsy

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. PD patients: All will meet criteria for probable PD, according to the new MDS Clinical Diagnostic criteria
2. Non-PD parkinsonism patients: They will have with progressive supranuclear palsy, multiple system atrophy, 'vascular parkinsonism' or corticobasal syndrome. All patients will have parkinsonism according to UK brain bank criteria, with a diagnosis of one of the above conditions made according to gold-standard expert evaluation. No patient will meet MDS Criteria for probable PD.
3. iRBD patients: All patients will have polysomnogram-confirmed RBD according to American Academy of Sleep Medicine Criteria. Patients will be free of parkinsonism and dementia according to neurological examination and will have no untreated sleep apnea, epilepsy, or other abnormalities that could cause dream enactment behavior.
4. Controls: These will be age matched (within 5 years) and sex-matched (with >90% concordance). All controls will have an examination confirming the absence of parkinsonism, and will have no symptoms of REM sleep behavior disorder, as assessed with the RBD1Q and expert interview.

Exclusion Criteria:

1. Diabetes Mellitus - In addition to causing autonomic neuropathy, hyperglycemia itself is known to interfere with results of the sudomotor scan
2. Any preceding diagnosis of autonomic neuropathy (of a cause other than PD)
3. Dementia of severity sufficient to preclude informed consent, MoCA <23.
4. Prescription of medications that directly alter peripheral autonomic function, including beta-blockers, sympatholytics (i.e. clonidine) and non-specific alpha-blockers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Parkinson's disease (PD) patients; 40 patients will be recruited. All will meet criteria for probable PD, according to the new MDS Clinical Diagnostic criteria. All participants will be 40 or older (young-onset PD includes many genetic causes, which often have normal autonomic function).	Device: Sudoscan and clinical assessment; The primary variable will be electrochemical skin conductance (ESC), as assessed by the SudoScan (Impeto Medical, France). The clinical assessment will include a neurological evaluation (including MDS-UPDRS), evaluation of autonomic symptoms and signs, EKG, evaluation of possible neuropathy and evaluation of non-motor variables.; Genetic: Skin biopsy; Evaluation of the denervation and synuclein deposition of skin biopsy
ACTIVE_COMPARATOR: parkinsonsism (non-PD) patients; 20 patients will also be recruited. These will include patients with progressive supranuclear palsy, multiple system atrophy, 'vascular parkinsonism' or corticobasal syndrome. All patients will have parkinsonism according to UK brain bank criteria, with a diagnosis of one of the above conditions made according to gold-standard expert evaluation. No patient will meet MDS Criteria for probable PD.	Device: Sudoscan and clinical assessment; The primary variable will be electrochemical skin conductance (ESC), as assessed by the SudoScan (Impeto Medical, France). The clinical assessment will include a neurological evaluation (including MDS-UPDRS), evaluation of autonomic symptoms and signs, EKG, evaluation of possible neuropathy and evaluation of non-motor variables.; Genetic: Skin biopsy; Evaluation of the denervation and synuclein deposition of skin biopsy
ACTIVE_COMPARATOR: idiopathic REM sleep behavior disorder patient; 40 patients will be recruited. All patients will have polysomnogram-confirmed RBD according to American Academy of Sleep Medicine Criteria. Patients will be free of parkinsonism and dementia according to neurological examination and will have no untreated sleep apnea, epilepsy, or other abnormalities that could cause dream enactment behavior.	Device: Sudoscan and clinical assessment; The primary variable will be electrochemical skin conductance (ESC), as assessed by the SudoScan (Impeto Medical, France). The clinical assessment will include a neurological evaluation (including MDS-UPDRS), evaluation of autonomic symptoms and signs, EKG, evaluation of possible neuropathy and evaluation of non-motor variables.; Genetic: Skin biopsy; Evaluation of the denervation and synuclein deposition of skin biopsy
PLACEBO_COMPARATOR: Controls; 40 controls will be age matched (within 5 years) and sex-matched (with >90% concordance). All controls will have an examination confirming the absence of parkinsonism, and will have no symptoms of REM sleep behavior disorder, as assessed with the RBD1Q and expert interview.	Device: Sudoscan and clinical assessment; The primary variable will be electrochemical skin conductance (ESC), as assessed by the SudoScan (Impeto Medical, France). The clinical assessment will include a neurological evaluation (including MDS-UPDRS), evaluation of autonomic symptoms and signs, EKG, evaluation of possible neuropathy and evaluation of non-motor variables.; Genetic: Skin biopsy; Evaluation of the denervation and synuclein deposition of skin biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Electrochemical skin conductance	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD severity-Hoehn and Yahr stage	PD severity will be assessed with the Hoehn and Yahr	up to 6 months
PD severity-MDS-UPDRS	PD severity will be assessed with the MDS-UPDRS	up to 6 months
Autonomic symptoms and signs		up to 6 months
EKG	Cardiac autonomic denervation will be assessed with analysis of heart rate variability on EKG	up to 6 months
Neuropathy	Patients will be screened for neuropathy with the 5-item peripheral neuropathy screening interview	up to 6 months
Non-motor symptoms associated with PD	Non-motor variables with be assessed with Parts I and II of the MDS-UPDRS	up to 6 months
Skin biopsy	Denervation and synuclein deposition of skin biopsy will include staining for proteinase-k-resistant synuclein (5C12 antibody) and neuronal markers to determine density of peripheral innervation	up to 12 months

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): June 1, 2018

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (ESTIMATE): May 10, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 30, 2018
• Last Update Submitted That Met QC Criteria: October 29, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: MP-CUSM-15-472

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified clinical data will be shared with the Michael J. Fox Foundation (the study funder) for Parkinson's research. These data may be kept for storage at a central repository either hosted by the Michael J. Fox Foundation, its collaborators, or consultants and will be kept indefinitely. In order to advance scientific discoveries, your de-identified data will be made publically available (with no personal identifying information) for the intended use of research in Parkinson's disease as well as other biomedical research studies that may not be related to Parkinson's disease.