An observational study in Parkinson Disease, Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), sponsored by Neuromed IRCCS. Recruiting at 1 site in Italy. Open to participants aged 20 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-18.
Sponsored by Neuromed IRCCS · Observational
Neurodegenerative disorders (NDDs), such as Parkinson¿s disease (PD), Alzheimer¿s disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are characterized by aggregation and intracellular accumulation of misfolded proteins, which are believed to play a key role in synaptic dysfunction and neuronal death. Protein structural complexes in biofluids have been proposed to mirror pathological conditions suggesting their use as biomarkers for NDDs characterized by protein aggregation. In this framework, we plan to: i) collect a large cohort of NDD and prodromal patients and healthy subjects using standardized clinical and genetics procedures; ii) apply a novel method based on genomics, proteomics and bioinformatic analysis to map protein complexes in biofluids; iii) identify novel circulating biomarkers and correlate them to genetic profiling and disease endophenotypes, and; iv) validate the biological properties in human brain tissue and dopaminergic cultures.
The project is a multicrentric observational study. Institutions involved are:
OU1 - IRCCS INM Neuromed OU2 -University of Piemonte Orientale The project takes advantage from the availability of a large collection of PD samples 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. induced pluripotent stem cells (iPSC) are available for 6 PD patients and 5 healthy subjects.
The activities of the Operating Unit (OU1) are:
The activities of the Operating Unit (OU2) are:
4,573 studies on the registry are indexed under Parkinson Disease; 1,086 are open to participants now.
This study's planned enrollment of 110 is above the median of 96 across 1,085 observational studies indexed under Parkinson Disease.
Browse Parkinson Disease studies →Neuromed IRCCS is the lead sponsor of 81 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The study will be performed on a total population of 510 subjects (140 PD, 150 AD/ALS/FTD, 120 controls, 100 relatives of patients carrying mutations), of these, 90 patients with a clinical diagnosis of neurodegenerative disease (40 PD cases, 30 AD cases, 20 ALS/FTD cases) will be recruited in this study. The study also includes the recruitment and analysis of 20 control individuals selected among those who will undergo CSF sampling in a diagnostic regimen for non-inflammatory and non-neurodegenerative diseases. The validation cohort, partially already available at the Clinical Centers involved in the study, is composed of 400 subjects of which: 100 PD patients (UO1), 100 AD/FTD/ALS patients (UO2), 100 healthy family members of NDD patients carrying pathogenic mutations and who have not yet developed the disease (UO1) and 100 control individuals (UO1).
For the IRCCS INM Neuromed, patients will be recruited from those affiliated with the Center for the Study and Treatment of Parkinson's Disease of the Neuromed Institute of Pozzilli. Affected subjects will be selected according to the criteria proposed by Gelb et al in 1999. This is a very pragmatic scheme based on the presence of four cardinal signs, the response to a test administration of Levodopa and the absence of atypical signs:
A) Presence of at least 2 of the 4 cardinal signs (tremor, rigidity, bradykinesia, asymmetric onset) one of which must be tremor or bradykinesia; B) Absence of atypical symptoms such as: i) early postural instability, freezing phenomena, cognitive deterioration, hallucinations, pathological involuntary movements, vertical gaze paralysis; ii) proven causes of secondary parkinsonism (focal lesions, drugs, toxic substances); C) Documented response to the use of L-dopa or dapamine agonists (or lack of an adequate therapeutic attempt with L-dopa or dopamine agonists).
Exclusion Criteria:
PD PATIENTS
AD/FTD/ALS PATIENTS
CONTROLS
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Genetic: whole genome sequencing PD 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
Genetic: whole genome sequencing AD Partecipants will be assessed for disease progression: * assessment of cognitive disorders (MMSE, MOCA test, clock test); * assessment of language disorders; * current drug therapy (and possible start date of treatment); * date of onset of cognitive disorders; * acquisition and assessment of imaging data where present (MRI, CT, PET). DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate AD genes
Genetic: whole genome sequencing ALS/FTD Partecipants will be assessed for disease progression: * clinical classification according to El Escorial - revised; * assessment of cognitive disorders (and classification according to Strong criteria, 2017); * assessment of language disorders; * ongoing pharmacological therapy (and possible start date of treatment); * date of onset of motor and cognitive disorders; * acquisition and assessment of imaging data where present (MRI, CT, PET). DNA of each partecipants we will analysed by whole genome sequencing by next generation sequencing to identify any variant in candidate ALS/FTD genes
motor symptoms of PD 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. Itincludes 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.
Time frame: 2 years
motor and non motor symptoms of PD 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 DailyLiving; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver
Time frame: 2 years
clinical evaluation of cognitive impairment of PD, AD, ALS/FTD patients
PD patients will be evaluated with the Montreal Cognitive Assessment (MoCA) test. This 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.- assessment of language disorders. ALS/FTD - assessment of cognitive disorders (and classification according to Strong criteria, 2017); - assessment of language disorders. AD patients: - assessment of cognitive disorders (MMSE, MOCA test, clock test); - assessment of language disorders.
Time frame: 2 years
clinical evaluation of ALS/FTD patients
Clinical classification according to El Escorial - revised
Time frame: 2 years
identification of variants/mutations
PD patients: 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. AD, ALS/FTD: deleterious variants (missense, non sense, frameshift and splicing) in responsible genes will be considered.
Time frame: 2 years
Identification of protein complexes in CSF
Protein complexes present in the CSF of PD/AD/FTD/ALS patients and control subjects recruited in the two Clinical Centers participating in the study will be analyzed by size exclusion chromatography (SEC) and by label-free proteomic analysis. The complexes will be separated and fractionated by SEC and identified and quantified by mass spectrometers. Statistical analysis will allow to identify the presence/absence or the different abundance of protein complexes in patients compared to controls and therefore the identification of biomarkers and potential therapeutic targets.
Time frame: 2 years
Bioinformatic analysis for the identification of proteins and molecular pathways involved
Through advanced bioinformatics analysis, multivariate statistical analysis techniques and machine learning, proteins and molecular pathways involved in different neurodegenerative diseases and their development will be identified. This will allow us to understand and improve the knowledge of these pathologies and to identify potential therapeutic or diagnostic targets/pathways.
Time frame: 2 years
Validation of protein complexes in plasma
The key marker protein complexes identified in Phase 1 will be validated in plasma samples from PD/AD/FTD/ALS patients and control subjects through targeted mass spectrometry analyses and through immunochemical technical analyses such as ELISA, Western blot and immunoassays.
Time frame: 2 years
Association analysis with endophenotypes
Correlation analyses will be aimed at evaluating whether the presence of aggregates impacts on the age of onset (AAO), neurological symptoms, non-motor symptoms, as well as the response to L-dopa treatment. In addition, genetic data from PD patients will be integrated with biomolecular data to identify altered molecular pathways. ROC curves will be used to evaluate the diagnostic power of the test.
Time frame: 2 years
Analysis of the biological impact of protein complexes identified in CSF on the viability of mdDA dopaminergic neurons obtained from iPSCs of patients and controls
Patient and control iPSC lines will be differentiated into mesodiencephalic dopaminergic neurons using published protocols. Cells will be exposed to protein aggregates purified from patient CSF and the cells' vulnerability to neurodegeneration will be assessed.
Time frame: 2 years
Plan to share: No
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Started Feb 2025 (actual). Primary completion is estimated for Aug 2026, 18 months after the start.
Of 378 non-industry observational studies under Parkinson Disease, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 133. This study's planned 18 months is below that.
Counting every sponsor, half of 438 studies reached it within 47 months; a quarter within 22 and three quarters within 114.
How these figures are worked out, and which studies are left out of them.
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