NCT06167603 is an observational prospective cohort study led by IRCCS San Raffaele (Milan, Italy) in collaboration with the IRCCS National Neurological Institute "C. Mondino" Foundation (Pavia, Italy). The study investigates the role of glucocerebrosidase (GBA) mutations in accelerating alpha-synuclein and synaptic pathologies in Parkinson's disease through combined neuroimaging (FDG-PET), biochemical, and clinical features[1].
The goal is to illuminate the pathophysiology underlying GBA mutations in PD, identify biomarkers for the malignant GBA-PD phenotype, and define a prognostic algorithm for predicting faster disease progression and monitoring disease trajectories in unaffected GBA mutation carriers[2].
| Field | Value |
|---|---|
| NCT ID | NCT06167603 |
| Status | RECRUITING |
| Study Type | Observational (Cohort, Prospective) |
| Start Date | April 30, 2023 (Actual) |
| Primary Completion | December 12, 2024 (Estimated) |
| Final Completion | April 1, 2026 |
| Enrollment | 140 participants (Estimated) |
| Study Design | Cohort study, three groups: GBA-PD, idiopathic PD (iPD), asymptomatic GBA carriers |
| Sponsor | IRCCS San Raffaele |
| Lead PI | Chiti Arturo, Professor in Diagnostic Imaging and Radiotherapy, Vita-Salute San Raffaele University |
The study recruits three distinct populations[3]:
This three-group design allows direct comparison of disease mechanisms and progression patterns between GBA-mediated and sporadic forms of PD[2:1].
Fluorodeoxyglucose positron emission tomography (FDG-PET) is the primary neuroimaging tool[4]. FDG-PET represents a unique tool to study early metabolic alterations associated with neurodegeneration, both at group and individual subject levels:
Blood sampling and standardized clinical assessments performed at three timepoints:
Clinical assessments likely include:
FDG-PET cerebral metabolism comparison: Measures cerebral metabolism differences between Parkinson's subjects with a mutation in the GBA gene (GBA-PD group) compared to patients with idiopathic Parkinson's[4:1].
While full secondary outcomes were not detailed in the available protocol data, the study description suggests these endpoints:
GBA mutations are the most common genetic risk factor for Parkinson's disease, with carriers showing a more malignant phenotype characterized by[@gba2024a; @gba2024b]:
The study is grounded in the well-established bidirectional relationship between glucocerebrosidase activity and alpha-synuclein aggregation[5]:
FDG-PET provides a window into the downstream metabolic consequences of this pathogenic loop, potentially revealing imaging biomarkers that precede clinical manifestations.
The study explicitly aims to move toward precision medicine for PD by:
Neurological Institute Foundation Casimiro Mondino
| Name | Role | Phone | |
|---|---|---|---|
| Micol Avenali | Principal Investigator / Contact | 0382.380221 | micol.avenali@mondino.it |
| Cinzia Fattore | Contact | 0382.380221 | cinzia.fattore@mondino.it |
| Arturo Chiti | Sub-Investigator | — | — |
| Silvia Paola Caminiti | Sub-Investigator | — | — |
This observational study complements several interventional trials targeting GBA in PD:
NCT06167603 provides mechanistic imaging data that could inform patient selection and outcome measures for these interventional approaches.
The study does not include individual participant data (IPD) sharing. No results are currently posted on ClinicalTrials.gov.
Migdalski L, et al. Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease. Translational Neurodegeneration. 2024. ↩︎ ↩︎
Pellegrini C, et al. GBA1-associated Parkinson's Disease Is a Distinct Entity. Annals of Neurology. 2024. ↩︎ ↩︎
Avenali M, et al. GBA1 Mutations and Parkinson's Disease: From Genetics to Disease Phenotype. Journal of Neurology. 2024. ↩︎
Mohan A, et al. Brain glucose metabolism in Parkinson's disease with and without GBA mutations. Neurobiology of Aging. 2020. ↩︎ ↩︎
Glucocerebrosidase and alpha-synuclein: A bidirectional relationship. Journal of Parkinson's Disease. 2023. ↩︎