Implementing a National Biobank of PD With WGS and Functional Assessment of Polygenic Inheritance by iPSC Technology

NCT05721911 | Recruiting

• 1 other identifier: PNRR-MAD-2022-12375960
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Parkinson Disease; REM Sleep Behavior Disorder

Outcome Measures

Primary Outcomes (8)

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

  The Hoehn and Yahr Scale will be used to measure how Parkinson's symptoms progress and the level of disability. It includes stages 1 through 5: Stage 1. Unilateral involvement only, usually with minimal or no functional impairment; Stage 2 = Bilateral disease, without impairment of balance; Stage 3 = Mild to moderate bilateral disease; some postural instability; physically independent. Stage 4 = Severe disability; still able to walk or stand unassisted. Stage 5 = Wheelchair bound or bedridden unless aided.

  2 years

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

  The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver

  2 years

• clinical evaluation of of sleep disorders in PD and RBD patients

  presence of sleep disorders will be evaluated by Munich Parasomnia Screening (MUPS)

  2 years

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

  Sleep microstructure will be evaluated by analysis of the alternating cyclic pattern (CAP), a marker of NREM sleep instability.

  2 years

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

  The Montreal Cognitive Assessment (MoCA) is a test used by healthcare providers to evaluate people with memory loss or other symptoms of cognitive decline. The MoCA contains 30 questions and checks different types of cognitive or thinking abilities. These include:orientation, short-term memory/delayed recall, executive function/visuospatial ability, clock-drawing test.

  2 years

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

  LID occurrence will be related to levodopa dosage and time of therapy

  2 years

• identification of variants/mutations

  the number of multiple rare (Minor allele frequency, MAF\<0.01) deleterious (missense, non sense, frameshift and splicing) variants in PD genes will be counted in PD patients and unrelated healthy subjects. Case-control assoiciation study will evaluate the PD risk

  2 years

• association with phenotypic manifestation of PD

  The presence of one or more variants will be tested for association with phenotypic manifestation of PD (motor, non motor, and cognitive signs, as well as age at onset, LID and neuroimaging changes) to assess the variant burden effect on progression, and prognosis of the disease

  2 years

Interventions

whole genome sequencing GENETIC

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

Eligibility Criteria

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

Study Population

The study includes 100 PD patients, 30 RBD and 100 age/gender-matched controls. All PD patients will be diagnosed at the IRCCS Neuromed and followed-up (at least for 3 years) for disease progression

You may qualify if:

• 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).
• Subjects affected by idiopathic RBD that will be selected according to the most recent criteria international classification of sleep disorders (ICSD-3).

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele

Milan, Italy, 20132, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for purification of DNA, plasma and serum and PBMC. hiPSC will be generated by reprogramming of PBMC.

MeSH Terms

Conditions

Parkinson Disease; REM Sleep Behavior Disorder

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Vania Broccoli, PhD

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vania Broccoli, PhD

CONTACT

+39 0226434616; broccoli.vania@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of CNR Unit

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 10, 2023
• Study Start: October 30, 2023
• Primary Completion: March 4, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

IT (1)