SudoScan as a Biomarker of Parkinson's Disease

Not Applicable

Completed

• Conditions: Parkinson's Disease
• Interventions: Device: Sudoscan and clinical assessment; Genetic: Skin biopsy

• Registration Number: NCT02767037
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-01-22
• Study First Submitted QC: 2016-05-06
• Study First Posted: 2016-05-10
• Study Start: 2016-06
• Primary Completion: 2017-12
• Study Completion: 2018-06
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-29
• Last Update Posted: 2018-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Controls	Skin biopsy	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.
Parkinson's disease (PD) patients	Sudoscan and clinical assessment	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).
parkinsonsism (non-PD) patients	Sudoscan and clinical assessment	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.
parkinsonsism (non-PD) patients	Skin biopsy	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.
Parkinson's disease (PD) patients	Skin biopsy	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).
idiopathic REM sleep behavior disorder patient	Skin biopsy	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.
idiopathic REM sleep behavior disorder patient	Sudoscan and clinical assessment	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.
Controls	Sudoscan and clinical assessment	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.

Primary Outcome Measures

Name	Time	Method
Electrochemical skin conductance	up to 6 months

Secondary Outcome Measures

Name	Time	Method
PD severity-MDS-UPDRS	up to 6 months	PD severity will be assessed with the MDS-UPDRS
Autonomic symptoms and signs	up to 6 months
PD severity-Hoehn and Yahr stage	up to 6 months	PD severity will be assessed with the Hoehn and Yahr
EKG	up to 6 months	Cardiac autonomic denervation will be assessed with analysis of heart rate variability on EKG
Neuropathy	up to 6 months	Patients will be screened for neuropathy with the 5-item peripheral neuropathy screening interview
Non-motor symptoms associated with PD	up to 6 months	Non-motor variables with be assessed with Parts I and II of the MDS-UPDRS
Skin biopsy	up to 12 months	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