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

NCT03043768 | Completed

• 1 other identifier: CAPTURE PD,Vs.02.0,06/29/2015
• Study Type: observational
• Target: 50
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Autonomic; Diagnosis; Pilomotor; Alpha-synuclein; Axon-reflex; Peripheral nerve fibers

Outcome Measures

Primary Outcomes (3)

• QPART Pilomotor Function Parameter - Number of goose bump impressions

  Mean difference in number of goose bump impressions compared between Cohort 1 (PD Patients) and Cohort 2 (healthy volunteers).

  36 months

• QPART Pilomotor Function Parameter - Mean area of goose bump impressions

  Mean area of goose bump impressions compared between Cohort 1 (PD Patients) and Cohort 2 (healthy volunteers).

  36 months

• QPART Pilomotor Function Parameter - Spatial spread of axon-reflex pilomotor response

  Spatial spread of axon-reflex pilomotor response compared between Cohort 1 (PD Patients) and Cohort 2 (healthy volunteers).

  36 months

Secondary Outcomes (3)

• Alpha-synuclein Ratio

  36 months

• Perceived Autonomic Symptoms

  36 months

• Motor Symptom Progression

  36 months

Other Outcomes (4)

• QDIRT Sudomotor Function Parameter - Number of Sweat droplets

  36 months

• QDIRT Sudomotor Function Parameter - Size of sweat droplets

  36 months

• QDIRT Sudomotor Function Parameter - Axon-reflex spread of sweat droplets

  36 months

Study Arms (2)

PD patients

Male and female PD patients (idiopathic parkinsonism, Hoehn and Yahr \[H\&Y\] scores 1-2) aged 35 to 80 years

Control subjects

Age-and gender matched healthy control subjects

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Male and female patients with early Parkinson's disease, gender matched healthy control subjects

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)

Sponsors & Collaborators

• GWT-TUD GmbH: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• Prothena Biosciences Limited: collaborator

Study Sites (4)

Center for Autonomic and Peripheral Nerve Disorders, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School

Boston, Massachusetts, 02215, United States

Location

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden

Dresden, Saxony, 01307, Germany

Location

Departement of Neurology, Charite University Medicine Berlin

Berlin, 13353, Germany

Location

Department of Neurology, Semmelweis University

Budapest, 1083, Hungary

Location

Related Publications (7)

• Wang N, Gibbons CH, Lafo J, Freeman R. alpha-Synuclein in cutaneous autonomic nerves. Neurology. 2013 Oct 29;81(18):1604-10. doi: 10.1212/WNL.0b013e3182a9f449. Epub 2013 Oct 2.

  PMID: 24089386 BACKGROUND

• Siepmann T, Gibbons CH, Illigens BM, Lafo JA, Brown CM, Freeman R. Quantitative pilomotor axon reflex test: a novel test of pilomotor function. Arch Neurol. 2012 Nov;69(11):1488-92. doi: 10.1001/archneurol.2012.1092.

  PMID: 22868966 BACKGROUND

• Freeman R. Autonomic peripheral neuropathy. Lancet. 2005 Apr 2-8;365(9466):1259-70. doi: 10.1016/S0140-6736(05)74815-7.

  PMID: 15811460 BACKGROUND

• Hu F, Jin J, Qu Q, Dang J. Sympathetic Skin Response in Amyotrophic Lateral Sclerosis. J Clin Neurophysiol. 2016 Feb;33(1):60-5. doi: 10.1097/WNP.0000000000000226.

  PMID: 26844971 BACKGROUND

• Gibbons CH, Illigens BM, Centi J, Freeman R. QDIRT: quantitative direct and indirect test of sudomotor function. Neurology. 2008 Jun 10;70(24):2299-304. doi: 10.1212/01.wnl.0000314646.49565.c0.

  PMID: 18541883 BACKGROUND

• Siepmann T, Arndt M, Sedghi A, Szatmari S Jr, Horvath T, Takats A, Bereczki D, Moskopp ML, Buchmann S, Skowronek C, Zago W, Woranush W, Lapusca R, Weidemann ML, Gibbons CH, Freeman R, Reichmann H, Puetz V, Barlinn K, Pinter A, Illigens BM. Two-Year observational study of autonomic skin function in patients with Parkinson's disease compared to healthy individuals. Eur J Neurol. 2023 May;30(5):1281-1292. doi: 10.1111/ene.15733. Epub 2023 Feb 24.

  PMID: 36773001 DERIVED

• Siepmann T, Pinter A, Buchmann SJ, Stibal L, Arndt M, Kubasch AS, Kubasch ML, Penzlin AI, Frenz E, Zago W, Horvath T, Szatmari S Jr, Bereczki D, Takats A, Ziemssen T, Lipp A, Freeman R, Reichmann H, Barlinn K, Illigens BM. Cutaneous Autonomic Pilomotor Testing to Unveil the Role of Neuropathy Progression in Early Parkinson's Disease (CAPTURE PD): Protocol for a Multicenter Study. Front Neurol. 2017 May 26;8:212. doi: 10.3389/fneur.2017.00212. eCollection 2017.

  PMID: 28603514 DERIVED

Related Links

• Michael J. Fox Foundation Grant Site of CAPTURE PD

Biospecimen

Retention: SAMPLES WITHOUT DNA

3mm skin biopsies (punch biopsies)

MeSH Terms

Conditions

Parkinson Disease; Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Timo Siepmann, MD

  Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden

  PRINCIPAL INVESTIGATOR

• Ben MW Illigens, MD

  Center for Autonomic and Peripheral Nerve Disorders, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: February 6, 2017
• Study Start: June 1, 2016
• Primary Completion: January 28, 2018
• Study Completion: January 28, 2018
• Last Updated: July 22, 2022

Record last verified: 2017-02

Locations

US (1); DE (2); HU (1)