SudoScan as a Biomarker of Parkinson's Disease

Study Overview
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Brief Summary
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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

Official Title
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SudoScan as a Biomarker of Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: Sudoscan and clinical assessment
* Genetic: Skin biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PD patients: All will meet criteria for probable PD, according to the new MDS Clinical Diagnostic criteria 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. 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. 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: Diabetes Mellitus - In addition to causing autonomic neuropathy, hyperglycemia itself is known to interfere with results of the sudomotor scan Any preceding diagnosis of autonomic neuropathy (of a cause other than PD) Dementia of severity sufficient to preclude informed consent, MoCA <23. Prescription of medications that directly alter peripheral autonomic function, including beta-blockers, sympatholytics (i.e. clonidine) and non-specific alpha-blockers.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Parkinson's disease (PD) patients<br>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<br>* 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.<br>Genetic: Skin biopsy<br>* Evaluation of the denervation and synuclein deposition of skin biopsy<br>|
| Active Comparator: parkinsonsism (non-PD) patients<br>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<br>* 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.<br>Genetic: Skin biopsy<br>* Evaluation of the denervation and synuclein deposition of skin biopsy<br>|
| Active Comparator: idiopathic REM sleep behavior disorder patient<br>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<br>* 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.<br>Genetic: Skin biopsy<br>* Evaluation of the denervation and synuclein deposition of skin biopsy<br>|
| Placebo Comparator: Controls<br>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<br>* 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.<br>Genetic: Skin biopsy<br>* Evaluation of the denervation and synuclein deposition of skin biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |