Clinical trial NCT06814431: Study on the Incidence of Malignant Neoplasms in Patients with Parkinson's Disease and Heterozygous Mutation of the GBA Gene
Official title: Study on the Incidence of Malignant Neoplasms in Patients with Parkinson's Disease and Heterozygous Mutation of the GBA Gene
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Idiopathic Parkinson&#39;s Disease (PD)
Keywords: Parkinson's Disease
Neoplasms
GBA1
Genetic Parkinson's Disease
Lead sponsor: Azienda USL Reggio Emilia - IRCCS
Sponsor class: OTHER_GOV
First posted: 2025-02-07
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be selected from a network of Italian neurology centers with extensive experience in studying GBA-associated PD, in collaboration with local cancer registries. The study will include approximately 3,000 consecutive PD patients, subdivided into 500 patients with GBA mutations and 2,500 patients with idiopathic PD.

These participants will be compared with data from cancer registries to investigate potential associations between GBA mutations and malignancies. The population is drawn from specialized movement disorder centers and represents a clinically well-characterized cohort with access to standardized diagnostic and follow-up procedures.

Brief summary: This multicenter retrospective observational study investigates the incidence of malignant neoplasms in Parkinson's disease (PD) patients carrying heterozygous pathogenic variants in the GBA1 gene. The study compares these patients to individuals with idiopathic PD and to the general population within a large national cohort.

The rationale for the study lies in the growing evidence indicating an increased risk of malignant neoplasms in patients affected by Gaucher disease.

The primary objective is to assess whether PD patients with GBA1 mutations have a higher incidence of malignant neoplasms compared to the general population. Secondary objectives include comparing the incidence of malignant neoplasms between GBA1-PD and idiopathic PD patients, as well as between idiopathic PD patients and the general population. Additionally, the study aims to characterize oncological conditions by sex, age, center, and tumor site, with specific attention to distinguishing hematologic tumors from solid tumors.

By identifying potential associations between GBA1 mutations and malignancies in PD, the findings could guide more comprehensive patient management, including screening for malignant neoplasms alongside Parkinson's disease care.

Detailed description: The study will involve a network composed by different Italian Movement Disorders Centres and the corresponding local cancer registries, responsible for the active collection of cancer cases. Data will be collected from approximately 3000 consecutive Parkinson's disease (PD) patients, including about 500 patients carrying GBA1 mutations and 2500 idiopathic PD. Data about the presence of malignancies will be extracted from the Local Cancer Registries for each patient.

Eligibility criteria: Inclusion Criteria:

* \>18 years
* Diagnosis of Parkinson's Disease through the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinson's Disease.

Exclusion Criteria:

* Uncertain diagnosis

Primary outcomes:
measure: Evaluation of Increased Incidence of Malignant Neoplasms in Parkinson's Disease Patients with GBA1 Mutation Compared to the General Population
timeFrame: From birth to a maximum of 36 months after enrollment
Secondary outcomes:
measure: Evaluation of Increased Incidence of Malignant Neoplasms in Parkinson's Disease Patients with GBA1 Mutation Compared to Non-Genetic Parkinson's Disease Patients
timeFrame: From birth to a maximum of 36 months after enrollment
measure: Evaluation of Increased Incidence of Malignant Neoplasms in Idiopathic Parkinson's Disease Patients Compared to the General Population
timeFrame: From birth to a maximum of 36 months after enrollment
measure: Description of Oncological Condition Incidence by Sex, Age, Center, and Tumor Site, with Specific Focus on Hematologic Versus Solid Tumors
timeFrame: From birth to a maximum of 36 months after enrollment
Other outcomes:
Locations:
city: Brindisi
country: Italy
facility: Ospedale A. Perrino
city: Milano
country: Italy
facility: IRCCS Istituto Neurologico Carlo Besta
city: Reggio Emilia
country: Italy
facility: Azienda USL IRCCS di Reggio Emilia
city: Trento
country: Italy
facility: Ospedale Santa Chiara di Trento
Study officials:
References:
citation: Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017 Feb 17;18(2):441. doi: 10.3390/ijms18020441.
citation: Mistry PK, Taddei T, vom Dahl S, Rosenbloom BE. Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism. Crit Rev Oncog. 2013;18(3):235-46. doi: 10.1615/critrevoncog.2013006145.