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

University of Aarhus

Status: Invitation-only

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

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT06745011

NNF230C0082689 (Other Grant/Funding Number)

1-10-72-20-24

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

100 participants in 2 patient groups

Idiopathic polyneuropathy with abnormal cardiac 123I-MIBG scintigraphy

Description:

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

Description:

Participants diagnosed with polyneuropathy, orthostatic hypotension or non-nocturnal blood pressure dip and normal cardiac 123I-MIBG scintigraphy