NCT06803784

Discovery and Validation of Protein Structural Complexes in Circulating Biofluids As Novel Biomarkers for Early Diagnosis, Prognosis and Therapeutic Management of Patients Affected by Neurodegenerative Disorders

Recruiting now Last updated 17 March 2025

What this trial tests

trial testing Genetic: whole genome sequencing in Parkinson Disease in 110 participants. Currently enrolling.

Timeline

4 February 2025

Primary endpoint
31 August 2026

1 December 2026

Quick facts

Lead sponsor	Neuromed IRCCS
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	110
Start date	4 February 2025
Primary completion	31 August 2026
Estimated completion	1 December 2026
Sites	1 location across Italy

Drugs / interventions tested

• Genetic: whole genome sequencing
• whole exome sequencing
• whole exome sequencing

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →
• Amyotrophic Lateral Sclerosis (ALS) — all drugs for Amyotrophic Lateral Sclerosis (ALS) →
• Frontotemporal Dementia (FTD) — all drugs for Frontotemporal Dementia (FTD) →
• Alzheimer's Disease (AD) — all drugs for Alzheimer's Disease (AD) →

Sponsor

Neuromed IRCCS

Who can join

20 and older, any sex, with Parkinson Disease or Amyotrophic Lateral Sclerosis (ALS). Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• motor symptoms of PD 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. 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 = Se
• motor and non motor symptoms of PD 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 DailyLiving; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver
• clinical evaluation of cognitive impairment of PD, AD, ALS/FTD patients
  Time frame: 2 years
  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, cl
• clinical evaluation of ALS/FTD patients
  Time frame: 2 years
  Clinical classification according to El Escorial - revised
• identification of variants/mutations
  Time frame: 2 years
  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
• Identification of protein complexes in CSF
  Time frame: 2 years
  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

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.