Parkinson DiseaseNCT05721911
Implementing a National Biobank of PD With WGS and Functional Assessment of Polygenic Inheritance by iPSC Technology
An observational study of Parkinson Disease and REM Sleep Behavior Disorder, run by IRCCS San Raffaele at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease, REM Sleep Behavior Disorder
- What is being tested?
- whole genome sequencing
- How many people
- 230 participants
- Where
- 1 siteItaly
- Study dates
- 30 Oct 2023to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele
Milan, Italy, 20132
Vania Broccoli, PhD, 0226434616, broccoli.vania@hsr.it
About this study
Official title: 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
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
Read the detailed description
The project is a multicentric observational study. Instuitutions involved are:
IRCCS Hospital San Raffaele, Milan Italy (coordinator Operating Unit (OU1)) IRCCS INM Neuromed, Pozzilli, (IS) Italy (Operating Unit (OU2)) IRCCS San Raffaele Roma, (Operating Unit (OU3)) The project takes advantage from the availability of a large collection of PD samples (~800) PD from familiar and sporadic cases, recruited at IRCCS Neuromed, for which we already collected and stored clinical information, genetic data as well as DNA, serum, plasma and peripheral blood mononuclear cells (PBMCs) for the entire study cohort.
The activities of the IRCCS INM Neuromed are:
- standardization of the clinical reporting, sample collection, storage and identification between the centers;
- recruitment of 100 PD patients, 30 RBD patients and 100 healthy subjects (patients' wives/husbands), to be carried out during the scheduled outpatient visits for these patients;
- whole genome sequencing (WGS) and bioinformatic analysis (in collaboration with OU1) of a selected cohort of PD patients (200 samples), negative for mutations/variants in PD candidate genes;
- WGS analysis of REM sleep behaviour disorder (RBD) prodromal patients as a model to identify early biomarker for PD;
- development of an innovative protocol for early diagnosis of PD based on the co-inheritance of multiple rare deleterious variants in PD genes;
- generation of induced pluripotent cell lines (iPSC) by reprogramming PBMCs from PD patients and familiar healthy donors.
After signed informed consent patients 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 behavior disease). Each patient and control will be subjected to peripheral blood sampling for the isolation of DNA, plasma, serum, PBMC. For a subset of patients induced pluripotent stem cells (iPSC) will be generated starting from PBMC.
Whole genome sequencing approach will be used to identify novel associated vatiants.
Extensive computational analysis will be planned to map the SNPs to regulatory regions controlling the expression of selected genes. This effort will provide the initial knowledge to draft the association between particular genomic SNPs and their combinations with sporadic PD. This endeavor is critical to advance our understanding of the genetic roots of PD and is in line with analogous ongoing international studies with whom will seek coordination. The success of this research will provide the means for developing predictive genetic testing and counselling of patients with PD and their families.
To increase the power analysis data will be analyzed including WES data of a cohort of 800 PD patients and 300 healthy subject already available at IRCCS INM Neuromed.
- Conditions
- Parkinson Disease, REM Sleep Behavior Disorder
- Being tested
- whole genome sequencing
- Medical subject headings
- Parkinson Disease, REM Sleep Behavior Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
whole genome sequencingGenetic
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
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 2 years
clinical evaluation of levodopa-induced dyskinesia (LID) in PD patients
LID occurrence will be related to levodopa dosage and time of therapy
Measured: 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
Measured: 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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start30 Oct 2023
- Primary completion4 Mar 2026
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vania Broccoli, IRCCS San Raffaele
- Investigators
- Vania Broccoli, PhD, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05721911
- Sponsor's protocol ID
- PNRR-MAD-2022-12375960
- Status last verified
- Mar 2026
- First submitted
- 30 Jan 2023
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: genetic data
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05721911
- Acronym / sponsor ID
- PNRR-MAD-2022-12375960
- Conditions
- Parkinson Disease, REM Sleep Behavior Disorder
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 30 Oct 2023 (actual)
- Primary completion
- 4 Mar 2026 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 10 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
The project is a multicentric observational study. Instuitutions involved are:
IRCCS Hospital San Raffaele, Milan Italy (coordinator Operating Unit (OU1)) IRCCS INM Neuromed, Pozzilli, (IS) Italy (Operating Unit (OU2)) IRCCS San Raffaele Roma, (Operating Unit (OU3)) The project takes advantage from the availability of a large collection of PD samples (~800) PD from familiar and sporadic cases, recruited at IRCCS Neuromed, for which we already collected and stored clinical information, genetic data as well as DNA, serum, plasma and peripheral blood mononuclear cells (PBMCs) for the entire study cohort.
The activities of the IRCCS INM Neuromed are:
- standardization of the clinical reporting, sample collection, storage and identification between the centers;
- recruitment of 100 PD patients, 30 RBD patients and 100 healthy subjects (patients' wives/husbands), to be carried out during the scheduled outpatient visits for these patients;
- whole genome sequencing (WGS) and bioinformatic analysis (in collaboration with OU1) of a selected cohort of PD patients (200 samples), negative for mutations/variants in PD candidate genes;
- WGS analysis of REM sleep behaviour disorder (RBD) prodromal patients as a model to identify early biomarker for PD;
- development of an innovative protocol for early diagnosis of PD based on the co-inheritance of multiple rare deleterious variants in PD genes;
- generation of induced pluripotent cell lines (iPSC) by reprogramming PBMCs from PD patients and familiar healthy donors.
After signed informed consent patients 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 behavior disease). Each patient and control will be subjected to peripheral blood sampling for the isolation of DNA, plasma, serum, PBMC. For a subset of patients induced pluripotent stem cells (iPSC) will be generated starting from PBMC.
Whole genome sequencing approach will be used to identify novel associated vatiants.
Extensive computational analysis will be planned to map the SNPs to regulatory regions controlling the expression of selected genes. This effort will provide the initial knowledge to draft the association between particular genomic SNPs and their combinations with sporadic PD. This endeavor is critical to advance our understanding of the genetic roots of PD and is in line with analogous ongoing international studies with whom will seek coordination. The success of this research will provide the means for developing predictive genetic testing and counselling of patients with PD and their families.
To increase the power analysis data will be analyzed including WES data of a cohort of 800 PD patients and 300 healthy subject already available at IRCCS INM Neuromed.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| whole genome sequencingPartecipants 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 | Genetic | – |
Primary outcome
motor symptoms of PD and RBD patients will be evaluated with Hoehn and Yahr (HY) score
Time frame: 2 years
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.
motor and non motor symptoms of PD and RBD patients will be evaluated with MDS-UPDRS
Time frame: 2 years
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
clinical evaluation of of sleep disorders in PD and RBD patients
Time frame: 2 years
presence of sleep disorders will be evaluated by Munich Parasomnia Screening (MUPS)
clinical evaluation of of sleep disorders in PD and RBD patients by Polysomnography
Time frame: 2 years
Sleep microstructure will be evaluated by analysis of the alternating cyclic pattern (CAP), a marker of NREM sleep instability.
clinical evaluation of cognitive impairment of PD and RBD patients by MoCA test score
Time frame: 2 years
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.
clinical evaluation of levodopa-induced dyskinesia (LID) in PD patients
Time frame: 2 years
LID occurrence will be related to levodopa dosage and time of therapy
identification of variants/mutations
Time frame: 2 years
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
association with phenotypic manifestation of PD
Time frame: 2 years
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Individual participant dataSharing planned: Undecided. genetic data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vania Broccoli, PhD principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease and REM Sleep Behavior Disorder, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vania Broccoli, PhD (+39 0226434616, broccoli.vania@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
motor symptoms of PD and RBD patients will be evaluated with Hoehn and Yahr (HY) score (time frame: 2 years). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.