An observational study in Parkinson Disease, Parkinsonian Disorders and Brain Disease, sponsored by Azienda USL Reggio Emilia - IRCCS. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-23.
Sponsored by Azienda USL Reggio Emilia - IRCCS · Observational
This observational study aims to systematically characterize a cohort of patients with early-stage Parkinson's disease (PD) attending the Movement Disorders Center of AUSL-IRCCS Reggio Emilia, Italy. PD is the second most common neurodegenerative disorder, affecting about 1% of individuals over 60 years of age. The project will explore clinical and biological differences between the recently proposed "Brain-First" and "Body-First" phenotypes of PD. Patients will undergo detailed clinical evaluation, neuroimaging, and biomarker assessments (including neurodegeneration and neuroinflammation markers). Particular attention will be given to the progression of axial and cognitive symptoms, which represent major contributors to disability.
Findings from this study are expected to improve early patient stratification, clarify disease mechanisms, and support the development of precision medicine strategies and future disease-modifying therapies.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting up to 1% of individuals over the age of 60. While treatment remains symptomatic and no disease-modifying therapies are currently available, increasing research efforts are focusing on precision medicine approaches and the identification of disease subtypes that may guide prognosis and therapy.
Historically, PD patients have been classified according to motor (tremor-dominant, akinetic-rigid, axial) and non-motor features (sleep disturbances, autonomic dysfunction, mood disorders, fatigue, pain, weight loss, cognitive impairment). Genetic classifications have also been introduced, with approximately 10-15% of patients carrying mutations such as GBA or LRRK2, which are associated with earlier onset and potentially more aggressive disease.
In the early 2000s, Braak and colleagues proposed a neuropathological staging system in which α-synuclein pathology progresses in a stereotypical pattern from peripheral to central structures. More recent clinical and pathological evidence, however, has challenged this model and led to the proposal of two distinct subtypes: Brain-First and Body-First. In Brain-First PD, pathology begins in the central nervous system and spreads to the autonomic system; in Body-First PD, pathology originates in peripheral structures such as the enteric nervous system, propagating rostrally to involve the brain. REM sleep behavior disorder (RBD) has emerged as a clinical marker of the Body-First subtype.
This study will systematically characterize patients with early-stage PD, combining detailed clinical evaluation with instrumental assessments including neuroimaging and blood-based biomarkers. In particular, the project will investigate whether Brain-First and Body-First phenotypes differ in terms of:
The overarching goal is to identify biological and clinical markers that distinguish PD subtypes, improve early stratification, and support the development of targeted, disease-modifying therapies.
4,573 studies on the registry are indexed under Parkinson Disease; 1,086 are open to participants now.
This study's planned enrollment of 150 is above the median of 96 across 1,085 observational studies indexed under Parkinson Disease.
Browse Parkinson Disease studies →Azienda USL Reggio Emilia - IRCCS is the lead sponsor of 93 studies on the registry; 26 are open to participants now.
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The study population will consist of patients with early-stage Parkinson's disease (PD) attending the Movement Disorders Center of AUSL-IRCCS Reggio Emilia. Eligible participants will be adults diagnosed with PD according to international clinical criteria, in the initial stages of the disease, and not yet affected by major motor or cognitive disability. Patients will be characterized from both a clinical and instrumental perspective, including motor and non-motor symptoms, genetic background, and biomarkers of neurodegeneration and neuroinflammation.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with early-stage Parkinson's disease without REM sleep behavior disorder (RBD), consistent with a Brain-First phenotype. These patients typically show early central dopaminergic deficits followed by peripheral involvement.
Other: Clinical assessments · Other: Phenotypic classification
Patients with early-stage Parkinson's disease with REM sleep behavior disorder (RBD) before or at motor onset, consistent with a Body-First phenotype. These patients are expected to show early peripheral involvement (e.g., cardiac MIBG denervation) preceding central dopaminergic loss.
Other: Clinical assessments · Other: Phenotypic classification
standardized neurological examination, motor and non-motor symptom scales, cognitive testing, and autonomic symptom questionnaires.
patients will be stratified into Brain-First and Body-First phenotypes based on the presence of RBD and instrumental findings.
Assessment of the progression of axial symptoms
Differences in quantitative parameters of gait (phase duration, root mean square of the acceleration of the trunk in x, y, z axes) assessed through the instrumented Timed Up and Go test (phases considered: overall iTUG, sit-to-stand, sitting, first turn, second turn, walking forward, return gait) between the brain-first and body-first groups at diagnosis and at subsequent annual follow-up visits (5-year follow-up) in OFF-medication and ON-Medication (both in single and dual task) conditions.
Time frame: baseline, 12, 24, 36,48, 60 months
Risk of falling in the two subgroups, brain-first and body-first
Assessment of possible differences in scores obtained on the Walking Handicap Scale (WHS) at baseline and at subsequent annual follow-up visits (5-year follow-up). The Walking Handicap Scale (WHS) measures walking ability and community mobility across six levels, from limited physiological walking to unrestricted social ambulation. Possible scores range from 1 (most limited walking ability) to 6 (fully independent walking in social environments); higher scores indicate better walking function.
Time frame: baseline, 12, 24, 36,48, 60 months
Risk of falling in the two subgroups, brain-first and body-first
Assessment of possible differences in scores obtained on the Hendrich II Fall Risk Model (HIIFRM) at baseline and at subsequent annual follow-up visits (5-year follow-up). The Hendrich II Fall Risk Model (HIIFRM) assesses fall risk using clinical variables including confusion/disorientation/impulsivity, symptomatic depression, altered elimination, dizziness, gender, use of antiepileptics or benzodiazepines, and performance on the "Get-Up-and-Go" test. Possible total scores range from 0 (lowest fall risk) upwards (commonly up to about 16 depending on version); higher scores indicate greater fall risk.
Time frame: baseline, 12, 24, 36,48, 60 months
Assessment of the progression of axial symptoms
Differences in quantitative parameters of balance (center of pressure mean position referred to the mid-point of the heels, area of the 95% confidence ellipse, sway mean velocities and root mean square displacements in the antero-posterior and medio-lateral directions) assessed through a static posturography test (with eyes open) between the brain-first and body-first groups at diagnosis and at subsequent annual follow-up visits (5-year follow-up) in OFF-medication and ON-Medication (both in single and dual task) conditions.
Time frame: baseline, 12, 24, 36,48, 60 months
Assessment of disease progression
Assessment of the differences in the MDS-UPDRS total scores (part I, II, III, IV) and subscores (tremor, bradykinesia, rigidity, postural instability and gait difficulty, gait, dyskinesia and fluctuations subscores) in the study population at baseline and at subsequent annual follow-up visits (5-year follow-up).
Time frame: baseline, 12, 24, 36,48, 60 months
Assessment of the progression of neurodegeneration and inflammatory biomarkers (neurofilaments, interferon-γ, cell-mediated anti-α-synuclein responses).
Assessment of the differences in neurodegeneration and inflammatory biomarkers (neurofilaments, interferon-γ, cell-mediated anti-α-synuclein responses) in a subset of 50 patients in the study population. Analysis of differences in neurofilament levels and cell-mediated responses at baseline and at subsequent annual follow-up visits (5-year follow-up).
Time frame: baseline, 12, 24, 36,48, 60 months
Brain MRI: analysis of differences in qualitative and quantitative parameters extrapolated at diagnosis.
Assessment of quantitative differences in the degree of cortical and subcortical atrophy (volumetric automated segmentation of cerebral regions with the Quibim Precision software® quantified as % of intracranial volume) in the study population assessed through volumetric 1.5 Tesla brain MRI at baseline.
Time frame: 24 months
Baseline Assessment of Nigrostriatal and Myocardial Denervation.
Semiquantitative assessment (heart to mediastinum ratio \[H/M\]) of differences in myocardial denervation in the study population through cardiac 123I-MIBG scintigraphy (early and delayed imaging)
Time frame: 24 months
Plan to share: Undecided
Ran from Sep 2024 to primary completion in Oct 2025, 13 months.
Of 378 non-industry observational studies under Parkinson Disease, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 133. This study's 13 months is below that.
Counting every sponsor, half of 438 studies reached it within 47 months; a quarter within 22 and three quarters within 114.
How these figures are worked out, and which studies are left out of them.
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Azienda USL Reggio Emilia - IRCCS