Prodromal Model of Parkinson's Disease Confined to The Peripheral Nervous System (Prompark)

Description of a method to detect Parkinson's disease or Parkinson's-like disease at an early stage (Prodromal Parkinson's Disease) where damage is still confined to the peripheral nervous system damage. Simultaneous collection of biological material to establish a biobank for use as prognostic biomarkers for the development of Parkinson's disease and other neurodegenerative diseases in which pathological alpha-synuclein deposits accumulate.

Study Overview

• Status: Enrolling by invitation
• Conditions: Lewy Body Disease; Multiple System Atrophy; Autonomic Failure; Lewy Body Dementia (LBD); Polyneuropathy; Rapid Eye Movement Sleep Behavior Disorder; Parkinson Disease (PD); REM Behavior Disorder; Cardiac Imaging; REM Sleep Behavior Disorder (iRBD); Alpha-Synucleinopathy

Detailed Description

Primary aim (baseline):

To assess the prevalence of isolated REM Sleep Behavior Disorder (iRBD) or REM sleep without atonia (RSWA) in patients with idiopathic polyneuropathy with as to without abnormal cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy (assessment of cardiac sympathetic innervation)

Secondary aim (baseline):

To assess the prevalence of Parkinson's Disease (PD), Dementia with Lewy bodies (DLB) and Multiple System Atrophy (MSA) in patients with idiopathic polyneuropathy.

Hypothesis (baseline):

iRBD is more prevalent in patients known with idiopathic polyneuropathy and abnormal sympathetic innervation of the heart (assessed by cardiac 123I-MIBG scintigraphy) as compared to normal cardiac sympathetic innervation.

Primary aim (5-follow-up):

To assess whether patients with idiopathic polyneuropathy develop RSWA, iRBD, PD, DLB or MSA over a periode of five years.

Hypothesis (5-follow-up):

Patients known with idiopathic polyneuropathy and abnormal sympathetic innervation of the heart (assessed by cardiac 123I-MIBG scintigraphy) will convert to RSWA, iRBD, PD, DLB or MSA more often than those with normal cardiac sympathetic innervation.

Methods:

Clinical evaluation in combination with questionnaires, multi-modal imaging methods and polysomnography.

(Assessment of neuropathy: Neuropathy Impairment Score - Lower Leg (NIS-LL), Utah Early Neurological Scale (UENS), Kumamoto Neurological Scale and autonomic function test including Tilt table Test, Valsalva Maneuver, Deep Breathing Test, The Quantitative sensory axon reflex test (QSART). Cognition: The Montreal Cognitive Assessment (MoCA), Trail making Test B (TMT-B). Motor function: MDS-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III). Multi-modal imaging: cardiac 123I-MIBG scintigraphy, PE2I-PET-CT, MR-neuromelanin. Sleep: REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), one-night video polysomnography (PSG).)

Statistics:

The researchers expect to enroll 100 participants with idiopathic polyneuropathy and orthostatic hypotension or abnormal 24-hour blood pressure measurement (non-nocturnal blood pressure dip) who have undergone cardiac 123I-MIBG scintigraphy. Based on preliminary results, the investigators expect that 1/3 (30 participants) will have abnormal cardiac MIBG scintigraphy (cases; suggested to have prodromal PD or DLB) and 2/3 (70 participants) with normal MIBG scintigraphy (controls). The prevalence of iRBD detected by video-PSG is assumed to be 5% in participants with normal cardiac MIBG scintigraphy and 35% in participants with abnormal MIBG scintigraphy. To achieve a power of 88%, 81 participants have to be included (54 with normal and 27 with abnormal cardiac MIBG scintigraphy). Power calculation was based on Fisher's exact-test. Fisher's exact test was used because of an expected small number of participants with video PSG-detected iRBD.

Biobank:

Simultaneously collection of body tissue/fluids: skin, blood, cerebrospinal fluid and faeces. Analysis of the levels of phosphorylated tau, total-tau and amyloid beta in cerebrospinal fluid is performed at baseline.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Denmark
  • Jutland
    • Aarhus, Jutland, Denmark, 8200
      • Institute of Clinical Medicine, Aarhus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with definite polyneuropathy (confirmed by nerve conductions study) diagnosed in Jutland, Denmark and orthostatic hypotension or non-nocturnal blood pressure reduction.

Description

Inclusion Criteria:

• Definite polyneuropathy without known etiology (idiopathic) AND orthostatic hypotension (active stand test) OR non-nocturnal blood pressure reduction (24 hour blood pressure measurement)

Exclusion Criteria:

• Known etiology of polyneuropathy
• A diagnosis of either dementia, Parkinson's disease, Dementia with Lewy Bodies or Multiple System Atrophy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Idiopathic polyneuropathy with abnormal cardiac 123I-MIBG scintigraphy; Participants diagnosed with polyneuropathy, orthostatic hypotension or non-nocturnal blood pressure dip and abnormal cardiac 123I-MIBG scintigraphy (cardiac sympathetic dysfunction)
Idiopathic polyneuropathy with normal cardiac 123I-MIBG scintigraphy; Participants diagnosed with polyneuropathy, orthostatic hypotension or non-nocturnal blood pressure dip and normal cardiac 123I-MIBG scintigraphy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with REM sleep behavior disorder (RBD)	RBD-status will be assessed by one-night video-polysomnography and REM Sleep Behavior Disorder Screening questionnaire (RBDSQ). Diagnosis of RBD according to American Academy of Sleep Medicine (AASM) criteria.	RBD-status is assessed at two time point: Baseline (at the time of enrollment) and 5-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Parkinson's Disease (PD) or related alpha-synucleinopathies (Dementia with Lewy bodies (DLB), Multiple System atrophy (MSA)), REM-Sleep without atonia (RSWA)	Diagnosis of Parkinson's Disease according to Movement Disorder Society (MDS) Clinical Diagnostic Criteria (Postuma et al., 2015) supported by dopamine transporter imaging (18F-PE2I-PET). Diagnosis of Dementia with Lewy bodies according to the Dementia with Lewy Bodies Consortium (Mckeith et al., 2017) Diagnosis of Multiple System Atrophy according to MDS Clinical Diagnostic Criteria (Whenning et al., 2022) REM-sleep without atonia (RSWA) is assessed by one-night video-polysomnography	Assessed at baseline (at the time of enrollment) and at 5-year follow-up

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Novo Nordisk A/S; Aarhus University Hospital
• Investigators: Principal Investigator: Astrid J. Terkelsen, MD, DrMedSc, PhD, Professor, Department of clinical medicine, Aarhus University and Department of Neurology, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2024
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Polyneuropathy; REM Sleep Behavior Disorder; Lewy Body Disease; Isolated Rapid Eye Movement Sleep Behavior Disorder; Idiopathic Polyneuropathy; Cardiac MIBG Scintigraphy; Prodromal Lewy Body Disease; Alpha-synucleinopathy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neuromuscular Diseases; Metabolic Diseases; Peripheral Nervous System Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; Sleep Wake Disorders; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Proteostasis Deficiencies; Primary Dysautonomias; Autonomic Nervous System Diseases; Parasomnias; Hypotension; REM Sleep Parasomnias; Synucleinopathies; Mental Disorders; Polyneuropathies; Parkinson Disease; Multiple System Atrophy; Shy-Drager Syndrome; Lewy Body Disease; Pure Autonomic Failure; REM Sleep Behavior Disorder
• Other Study ID Numbers: 1-10-72-20-24; NNF230C0082689 (Other Grant/Funding Number: The Ascending Investigator, Novo Nordisk Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No