Clinical trial

Implementing a National Biobank of Genetic, Sporadic and Prodromic Parkinson's Disease With Whole Genome Analysis and Functional Assessment of Polygenic Inheritance by iPSC Technology

NCT05721911

Name

PNRR-MAD-2022-12375960

Description

The genetic complexity and heterogeneity of the sporadic forms of Parkinson's disease (PD) are posing a formidable challenge to disentangle their direct molecular causes. To advance this research, we plan to coordinate our local biorepositories of PD biological specimens creating a standardized and integrated national resource. In this framework, we plan to collect more samples from additional sporadic PD cases and to extend the sampling to patients with REM sleep behavior disease. We plan a large campaign of whole genome sequencing including about 200 patients to identify rare genomic variants plausibly associated with these diseases. In addition, we will standardize the generation and quality control of iPSC lines to make available to the scientific community. Finally, we will combine iPSC technology and gene editing to functionally assess the relative impact of rare variants in coding regions inherited together as a polygenic trait previously identified in selected sporadic PD cases

Trial arms

Trial start

2023-06-01

Estimated PCD

2025-05-01

Trial end

2025-05-01

Status

Not yet recruiting

Treatment

whole genome sequencing

Partecipants will be assessed for disease progression: Stadio di Hoehn and Yahr, MDS-UPDRS part III, MOCA test, no motor symptoms, therapy and LID occurrence, Sleep disorders. Partecipants will be subjected to peripheral blood sampling for the purification of DNA, plasma, serum, PBMC and generation of hiPSC. DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate PD genes

Size

230

Primary endpoint

motor symptoms of PD and RBD patients will be evaluated with Hoehn and Yahr (HY) score

2 years

motor and non motor symptoms of PD and RBD patients will be evaluated with MDS-UPDRS

2 years

clinical evaluation of of sleep disorders in PD and RBD patients

2 years

clinical evaluation of of sleep disorders in PD and RBD patients by Polysomnography

2 years

clinical evaluation of cognitive impairment of PD and RBD patients by MoCA test score

2 years

clinical evaluation of levodopa-induced dyskinesia (LID) in PD patients

2 years

identification of variants/mutations

2 years

association with phenotypic manifestation of PD

2 years

Eligibility criteria

Inclusion Criteria PD patients: * Presence of at least 2 of the 4 cardinal signs (tremor, rigidity, bradykinesia, onset asymmetric) one of which must be tremor or bradykinesia; * Absence of atypical symptoms such as: i) early postural instability, freezing phenomena, cognitive impairment, hallucinations, pathological involuntary movements, vertical gaze paralysis; ii) confirmed causes of secondary parkinsonism (focal lesions, drugs, substances toxic); * Documented response to L-dopa or dopamine agonist use (or lack of adequate therapeutic attempt with L-dopa or dopamine agonists). Inclusion Criteria RBD patients: • Subjects affected by idiopathic RBD that will be selected according to the most recent criteria international classification of sleep disorders (ICSD-3). Exclusion Criteria: * pre-existing psychiatric conditions; * Neurodegenerative neurological diseases such as multiple sclerosis, lateral sclerosis amyotrophic, Alzheimer's, neuromuscular pathologies, epilepsy; * diagnosis of dementia; * depression; * prolonged intake of anxiolytics, antidepressants, antipsychotics, hypnotic drugs, cognitive stimulants

Protocol

{'studyType': 'OBSERVATIONAL', 'patientRegistry': False, 'designInfo': {'observationalModel': 'CASE_CONTROL', 'timePerspective': 'PROSPECTIVE'}, 'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples for purification of DNA, plasma and serum and PBMC. hiPSC will be generated by reprogramming of PBMC.'}, 'enrollmentInfo': {'count': 230, 'type': 'ESTIMATED'}}

Updated at

2023-02-15

1 organization

1 product

2 indications

Organization

Neuromed IRCCS

Product

Whole Genome Sequencing

Indication

Parkinson's disease

Indication

REM Sleep Behavior Disorder