Cutaneous Autonomic Pilomotor Testing to Unveil the Role of Neuropathy Progression in Early Parkinson's Disease

Completed

Conditions studied: Parkinson's Disease

In brief

In Parkinson's disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. The investigators recently introduced a non-invasive technique to assess autonomic adrenergic fiber function using the quantitative pilomotor axon-reflex test (QPART). In the present study the investigators aim to assess the association between alpha-synuclein mediated structural autonomic nerve fiber damage and nerve function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test (QPART) and sudomotor function via quantitative direct and indirect test of sudomotor function (QDIRT). A prospective controlled study will be conducted in four sites (Dresden, Germany; Berlin, Germany; Budapest, Hungary; Boston, USA). A total of 52 male and female patients with idiopathic PD (Hoehn\&Yahr 1-2) and 52 age- and sex-matched healthy controls will be recruited. Pilomotor function will be evaluated after iontophoresis of phenylephrine on the dorsal forearm to elicit a cutaneous axon-reflex mediated response (goosebumps). Silicone impressions of the stimulated area will be obtained, scanned and quantified for pilomotor muscle impressions by number, impression size and area of axon-reflex pilomotor erection spread. Sudomotor function will be evaluated after axon-reflex stimulation via iontophoresis of acetylcholine on the dorsal forearm. Stained sweat droplets will be captured using repeated digital photography and will be quantified over time for droplet number and axon-reflex spread. Sympathetic skin responses following deep inspiration will be analyzed using skin conductance quantification. Testing and evaluation of autonomic and motor symptoms will be performed at baseline, after 2 weeks, 1 year, 2 years and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation. The investigators expect that this study will unveil whether progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition in PD. Additionally, potential applications of the used techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.

Key facts

Study ID

NCT03043768

Run by

GWT-TUD GmbH

People needed

50

Starts

2016-06-01

Expected to finish

2018-01-28

Last updated by the study team

2022-07-22

Who can join

Age: 35 and older, up to 80. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Male and female PD patients (idiopathic parkinsonism, Hoehn and Yahr [H\&Y] scores 1-2) aged 35 to 80 years and age-and gender matched healthy control subjects

You may not qualify if…

• any dermatological disorders affecting the cutaneous testing regions
• treatment with tricyclic antidepressants, noradrenergic antidepressants, beta-blockers, alpha-adrenergic agonists or antagonists, cholinergic or anti-cholinergic agents
• known allergy to phenylephrine or acetylcholine
• elevated alcohol consumption (more than 4 alcoholic beverages/week)
• nicotine consumption within the past 5 years
• known disorders affecting autonomic functions (including diabetes, pure autonomic failure, inflammatory demyelinating polyradiculoneuropathies, multiple system atrophy, atypical Parkinson syndromes, body mass index over 25 kg/m2, acute or chronic renal disease, gout, rheumatoid arthritis, Lupus, Sjogren 's syndrome, Triple- A syndrome, autonomic neuropathies not related to PD)

Where it is running

• Center for Autonomic and Peripheral Nerve Disorders, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School — Boston, Massachusetts, United States
• Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden — Dresden, Saxony, Germany
• Departement of Neurology, Charite University Medicine Berlin — Berlin, Germany
• Department of Neurology, Semmelweis University — Budapest, Hungary

Full record on ClinicalTrials.gov

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