Predicting Parkinson's Disease Before It Strikes: A Brain Imaging Study in At-Risk Individual

NCT07729748 | Active Not Recruiting

• 1 other identifier: RF-2018-12366746
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to characterize neurodegeneration progression in patients with polysomnography (PSG)-confirmed longstanding idiopathic REM sleep behavior disorder (iRBD) and to develop a prognostic model for clinical evolution and earlier identification of cases at risk of short-term conversion to clinically defined Parkinson's disease (PD). The study uses a multiparametric approach combining longitudinal clinical, neuropsychological, quantitative PSG, and multiparametric brain MRI markers (structural MRI, diffusion tensor imaging, resting-state functional MRI) to track neurodegeneration from the prodromal stage of PD and predict individual disease evolution. 50 patients with PSG-confirmed iRBD (duration since diagnosis greater than or equal to 5 years) and 50 age- and sex-matched healthy controls will be assessed at baseline and every year for 3 years at IRCCS Ospedale San Raffaele, Milan, Italy.

Conditions

Idiopathic REM Sleep Behavior Disorder; Parkinson Disease; Neurodegeneration; Prodromal Parkinson Disease

Keywords

REM sleep behavior disorder; iRBD; Parkinson's disease; Neurodegeneration; MRI; Polysomnography; Prodromal Parkinson; Diffusion tensor imaging; Resting-state fMRI; Prognostic model; Cognitive assessment

Outcome Measures

Primary Outcomes (3)

• Development of a prognostic model for conversion from iRBD to clinically defined Parkinson's disease

  A prognostic model based on longitudinal clinical markers for earlier identification of iRBD cases at risk of short-term conversion to clinically defined Parkinson's disease (PD).

  Baseline, 12 months, 24 months, and 36 months

• Development of a prognostic model for conversion from iRBD to clinically defined Parkinson's disease

  A prognostic model based on longitudinal neuropsychological markers for earlier identification of iRBD cases at risk of short-term conversion to clinically defined Parkinson's disease (PD).

  Baseline, 12 months, 24 months, and 36 months

• Development of a prognostic model for conversion from iRBD to clinically defined Parkinson's disease

  A prognostic model based on longitudinal PSG markers for earlier identification of iRBD cases at risk of short-term conversion to clinically defined Parkinson's disease (PD).

  Baseline, 12 months, 24 months, and 36 months

Secondary Outcomes (11)

• Longitudinal change in neuropsychological performance (MMSE)

  Baseline, 12 months, 24 months, and 36 months

• Longitudinal change in motor performance (Five Times Sit-To-Stand)

  Baseline, 12 months, 24 months, and 36 months

• Longitudinal change in motor performance (Ten-Meter Walking Test)

  Baseline, 12 months, 24 months, and 36 months

• Longitudinal change in motor performance (Timed Up and Go Test)

  Baseline, 12 months, 24 months, and 36 months

• Longitudinal change in motor performance (TUG with Cognitive Task)

  Baseline, 12 months, 24 months, and 36 months

Study Arms (2)

Patients with iRBD

50 patients with polysomnography (PSG)-confirmed longstanding idiopathic REM sleep behavior disorder (iRBD), with iRBD duration since diagnosis equal or greater than 5 years, without a clinically defined Parkinson's disease. Recruited from outpatient patients of the Department of Neurology, San Raffaele Hospital, Turro, Milan.

Other: Multiparametric clinical, neuropsychological, PSG and MRI assessment

Healthy Controls

50 healthy subjects similar for age (range 50-75 years old) and sex to patients with iRBD, recruited among non-consanguineous relatives, institute personnel and by word of mouth. They undergo PSG at study entry to exclude sleep disorders.

Other: Multiparametric clinical, neuropsychological, PSG and MRI assessment

Interventions

Multiparametric clinical, neuropsychological, PSG and MRI assessment OTHER

All participants undergo multiparametric longitudinal assessments at baseline and every year for 3 years, including: clinical and neuropsychological evaluation, motor assessment using inertial sensors, quantitative polysomnography (PSG) recording, and multiparametric brain MRI on a 3.0 Tesla system (Ingenia CX Philips) including 3D T1-weighted structural MRI, diffusion tensor (DT) MRI, and resting-state fMRI. Healthy controls undergo PSG at baseline only (to exclude sleep disorders) and motor, neuropsychological and MRI assessments at baseline and every year for 3 years.

Healthy Controls; Patients with iRBD

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with PSG-confirmed longstanding iRBD (duration since diagnosis greater than or equal to 5 years) recruited from outpatient patients of the Department of Neurology, San Raffaele Hospital, Turro, Milan, Italy. Healthy controls recruited among non-consanguineous relatives, institute personnel and by word of mouth.

You may qualify if:

• Right-handed participants.
• Monolingual native Italian speakers.
• Age between 50 and 75 years old.
• Normal or corrected-to-normal visual acuity.
• Mini Mental State Examination (MMSE) score greater than 24.
• Oral and written informed consent to study participation.
• Diagnosis of iRBD based on International Classification of Sleep Disorders, 3rd Edition (ICSD-3) criteria: presence of REM sleep without atonia; presence of sleep-related injurious-disruptive behaviors by history or abnormal sleep behaviors documented during PSG monitoring; absence of EEG epileptiform activity during REM sleep; presence of sleep disturbance not better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, or substance use disorder.
• PSG-confirmed iRBD duration since diagnosis equal or greater than 5 years.
• Absence of clinically defined Parkinson's disease.

You may not qualify if:

• Secondary forms of RBD on the basis of historical data, neurologic examination, and cerebral MRI findings.
• History of other systemic, neurologic, or psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations visible at MRI scan.
• Alcohol and/or psychotropic drugs abuse.
• Contraindications to MRI scan (cardiac pace-maker or other types of cardiac catheters, splinters or metallic shards, metallic prosthesis not compatible with the magnetic field generated by MRI, claustrophobia).
• Sleep disorders on the basis of clinical evaluation.
• History of systemic, neurologic, or psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations visible at MRI scan.
• Alcohol and/or psychotropic drugs abuse.
• Contraindications to MRI scan (cardiac pace-maker or other types of cardiac catheters, splinters or metallic shards, metallic prosthesis not compatible with the magnetic field generated by MRI, claustrophobia).
• Hypnotic or benzodiazepine medication.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (2)

San Raffaele Hospital - Sleep Disorders Center, Department of Neurology, Turro

Milan, Milano, 20127, Italy

Location

San Raffaele Neurology Unit - Neuroimaging Research Unit

Milan, Milano, 20132, Italy

Location

MeSH Terms

Conditions

Parkinson Disease; Nerve Degeneration; REM Sleep Behavior Disorder

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; REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Mental Disorders

Study Officials

• Massimo Filippi

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 28, 2026
• Study Start: December 4, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 28, 2026

Record last verified: 2026-07

Locations

IT (2)