Exploring Brain Molecular Imaging and Blood Biomarkers in Subjects With Glucocerebrosidase Mutations: Toward a Precision Medicine Approach to Characterize Parkinson's Disease Clinical Trajectories

NCT06167603 | Recruiting DMC

• 1 other identifier: GR-2021-12373993
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Glucocerebrosidase (GBA) mutations are the most common risk factor for Parkinson's Disease (PD). GBA-related PD(GBA-PD) exhibits a more malignant phenotype as compared to no-carriers. Still, the mechanisms behind the increased malignancy in GBA-PD are not well understood. The definition of biomarkers able to stratify PD clinical trajectories in PD is therefore crucial to identify effective treatments and support diagnosis.The investigators will examine the role of GBA-mutations in accelerating a-synuclein (a-syn) and synaptic pathologies in PD by combining neuroimaging (positron emission tomography-PET), biochemical and clinical features. This will illuminate the pathophysiology underlying GBA-mutations in PD and identify biomarkers for the malignant PD phenotype. Also, the investigators will combine longitudinal clinical and imaging/biochemical features to define a prognostic algorithm for predicting disease faster progression in GBA-PD and monitoring disease trajectories in unaffected GBA carriers.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• FDG-PET to measure cerebral metabolism between Parkinson's subjects with a mutation in GBA gene (MP-GBA) compared to patients with idiopathic Parkinson's.

  Differences in expression levels of posterior cerebral metabolism between Parkinson's patients with GBA mutation and idiopathic Parkinson's patients.

  3 years

Interventions

FDG-PET DIAGNOSTIC_TEST

Among other neuroimaging techniques, FDG-PET represents a unique tool to study the early metabolic alterations associated with neurodegeneration, both at the group and individual subject level.

Blood test and clinical examination. DIAGNOSTIC_TEST

baseline, 12-months and 24 months.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

PD patients with and without GBA mutations and asymptomatic GBA mutation carriers, relatives of GBA-PD patients.

You may qualify if:

• PD diagnosis according to MDS-PD criteria and for GBA-PD group, presence of heterozygous GBA mutations;
• disease duration 3-7years.

You may not qualify if:

• other neurological or systemic diseases;
• presence of mutations in another PD gene;
• impossibility or unwillingness to perform FDG-PET.

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• IRCCS National Neurological Institute "C. Mondino" Foundation: collaborator

Study Sites (1)

Neurological Institute Foundation Casimiro Mondino

Pavia, Italy

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Hematologic Tests; Physical Examination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Central Study Contacts

Micol Avenali

CONTACT

0382.380221; micol.avenali@mondino.it

Cinzia Fattore

CONTACT

0382.380221; cinzia.fattore@mondino.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Diagnostic Imaging and Radiotherapy Faculty of Medicine and Surgery, Vita-Salute San Raffaele University Director, Department of Nuclear Medicine, IRCCS Ospedale San Raffaele

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 12, 2023
• Study Start: April 30, 2023
• Primary Completion: December 12, 2024
• Study Completion: April 1, 2026
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)