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Enrolling by Invitation

NCT Number: NCT06875739

An Innovative Method in SAliva Samples for the Early Differential Diagnosis of High-impact NeuroDegenerative Diseases Through Raman Spectroscopy

The aim of the study is to validate a salivary test that allows for rapid and accurate objective diagnosis in the context of neurodegenerative diseases, a complex of diseases that includes Alzheimer's Dementia, Frontotemporal Dementia, Parkinson's Disease, Atypical Parkinsonisms, and Amyotrophic Lateral Sclerosis. In particular, the study aims to validate the salivary method against methods already in use (CSF method) or better studied (blood-based method) to allow early recognition of the disease condition and a distinction between the various diseases in order to receive appropriate therapy when possible.

In fact, the term neurodegenerative diseases is a broad term that includes disorders characterized by predominantly cognitive, motor, or mixed disorders for which early and accurate diagnosis of the disease is often difficult given also the variability with which these diseases can present. Ab initio recognition of a specific neurodegenerative disease would allow better pharmacological management of this disorder and facilitate the planning of care and rehabilitation interventions. In general, the recognition of neurodegenerative diseases could be facilitated by the use of a biomarker, which is a biological indicator that can be related to the onset or development of a disease. For this reason, it is necessary to compare the biomarker assay of patients with that of controls, so you were asked to participate as a "Control Subject" precisely because you do not have neurodegenerative disease.

Participation in the study involves, in addition to the collection of clinical-demographic data, the performance of a cognitive screening test to attest that your cognitive performance is in the normal range and the collection of biological blood and salivary samples, to be compared with those of participants with neurodegenerative diseases. Apolipoprotein E (ApoE) polymorphism study will be performed on the blood. A genetic polymorphism is a variation in the DNA sequence present in at least 1% of the population, the determination of ApoE polymorphism will allow to define a His genetic characteristic related to a higher or lower risk of developing Alzheimer's Disease. Two specific biomarkers, called neurofilament light chain (NfL) and gliofibrillary acidic protein (GFAP), namely a marker of neurodegeneration and one of neuroinflammation, will also be assayed on blood. Analysis of some inflammatory proteins called cytokines will also be performed.

On saliva, the biochemical composition will be evaluated with the analysis of particles present within it called vesicles by a method called Raman Spectroscopy, and the assay of specific biomarkers called NfL and GFAP will also be performed on saliva. The diagnosis of pathology made according to clinical diagnostic criteria and supported, when necessary, by the presence of recognized biomarkers (molecular imaging/liquid markers) will be used as a reference to evaluate the diagnostic capabilities of salivary methodology to detect different pathologies and to differentiate a pathological condition from Controls. Finally, the study will also include a comparison of salivary study methods on a group of people who are at a very early stage of disease, in order to detect whether the study performed with portable instrumentation is as good a method as that with laboratory instrumentation. In fact, the use of portable instrumentation would make it even easier to acquire a biomarker quickly directly from the clinic.

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Key information

Conditions

Neurodegenerative Disorders Alzheimer Disease Amyotrophic Lateral Sclerosis Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Dementia Fronto-Temporal Dementia Mental Disorders Metabolic Diseases Motor Neuron Disease Movement Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Parkinson Disease Parkinsonian Disorders Proteostasis Deficiencies Spinal Cord Diseases Synucleinopathies TDP-43 Proteinopathies Tauopathies

Age range

60 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Azienda Ospedaliera Universitaria di Cagliari, Cagliari, Italy

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

FOR ALL SUBJECTS: between 60 and 85 years old

FOR CASE:

  • ADD: diagnosis of dementia due to AD according to clinical criteria and supported by amyloid biomarkers (biomarkers in CSF or brain PET scan with amyloid-specific tracer) according to the definition biological or neurochemical definition of disease.
  • FTD: diagnosis of FTD-bv (behavioral variant) according to current clinical criteria.
  • PD: diagnosis according to MDS criteria; stable drug treatment (last 4 weeks).
  • APs: clinical diagnosis of Progressive Supranuclear Palsy according to the criteria of Hoglinger 2017, Corticobasal Degeneration according to the criteria of Armostrong 2013, Multisystem Atrophy according to the criteria of Wenning 2022.
  • ALS: clinical diagnosis according to the criteria of Brooks (2000) and subsequent revisions.

FOR CONTROL SUBJECTS

  • subjects admitted to IRCCS Don Gnocchi Florence in the departments of cardiology, pulmonology, orthopedics
  • ABSENCE of neurological symptoms
  • ABSENCE OF diagnosis of neurological or psychiatric diseases.
  • absence of positive family history (relatives I and II degree) for NDDs.
  • condition of clinical stability
  • at least 15 days after the acute event causing hospitalization.

FOR PRODROMAL CASE

  • Prodromal PD according to Berg's criteria.
  • prodromal FTD-bv according to Barker's criteria
  • prodromal AD according to the criteria of Dubois and Albert

Exclusion criteria

FOR CASE

  • Vascular Parkinsonism and other forms of secondary Parkinsonism such as drug-induced, other known or suspected causes (metabolic, brain tumor, etc.).
  • MoCA<15 for subjects with PD
  • cases with validated biomarkers (CSF and PET) in diagnostic conflict.

FOR ALL SUBJECTS

  • significant comorbidities
  • presence of severe systemic diseases or previously diagnosed psychiatric illnesses
  • patients unable to express consent for participation in the study themselves
  • presence of clinically unstable oral cavity disease (inflammatory/infectious)
  • time since acute event (if it occurred) <15 days
  • presence of local or systemic infection/inflammation detected on routine examinations.

Treatment and study plan

Primary outcomes

  1. Cumulative Illness Rating Scale (CIRS)

    Time frame: at enrollment

    it's a scale that records the comorbidity

  2. Neurological Clinical informations

    Time frame: at enrollment

    Presence/absence of symptoms/signs such as presence of speech disorder, hearing loss, low vision, dysphagia, oculomotricity disorder, disorientation, decreased insight, fatuity, perseveration/affacceleration, dx/sn recognition inability, gait disorder, instability/falls, neglect, ideomotor apraxia, signs of frontal release, rigidity/spasticity, bradykinesia, tremor or other involuntary movements, signs of first or second motor neuron, need for use of aids/presence of medical aids.

  3. Genetic test

    Time frame: at enrollment

    genetic testing will lead in NDDs and CTRL to the determination of the ApoE polymorphism (categorical variable). In NDDs, diagnostic investigation will aim to confirm/exclude a mutation in one of the disease-causing genes (APP, PS1, PS2, MAPT, PGRN, C9ORF72, SOD 1, TARDBP, VCP) in accordance with the pathological phenotype

  4. Plasma test

    Time frame: at enrollment

    NfL and GFAP assay result on plasma (continuous numeric variables)

  5. Salivary test

    Time frame: at enrollment

    results of NfL and GFAP assay on saliva (continuous numeric variables)

  6. nerological objective examination checklist

    Time frame: at enrollment

    presence/absence of symptoms/signs such as presence of speech disorder, hearing impairment, low vision, dysphagia, oculomotor disorder, disorientation, decreased insight, fatuity, perseveration/affacility, dx/sn recognition inability, gait disorder, instability/falls, neglect, ideomotor apraxia, signs of frontal release, rigidity/spasticity, bradykinesia, tremor or other involuntary movements, signs of first or second motor neuron,need for use of aids/presence of medical aids (categorical variables)

  7. UPDRS part III and IV

    Time frame: at enrollment

    evaluation of motor symptoms only for subjects with parkinson's disease or parkinsonisms

  8. Hoehn and Yahr Scale

    Time frame: at enrollment

    evaluation of clinical status only for subjects with parkinson's disease

  9. NON-MOTOR SYMPTOMS SCALE

    Time frame: at enrollment

    evaluation of non motor symptoms only for subjects with parkinson's disease

  10. Functional Rating Scale-Revised (ALSFRS-R)

    Time frame: at enrollment

    evaluation of disability only for subjects with ALS

  11. MONTREAL COGNITIVE ASSESSMENT (MOCA)

    Time frame: at enrollment

    Cognitive screening test for all except control subjects

  12. denomination test of SAND

    Time frame: at enrollment

    denomination of visual stimuli for all subjects except control cases

  13. semantic, phonemic and alternate fluency Test

    Time frame: at enrollment

    semantic, phonemic and alternate fluency Test for all subjects except control cases

  14. TRAIL MAKING TEST part A and B

    Time frame: at enrollment

    evaluation of attentional skills for all subjects except control cases

  15. STROOP TEST

    Time frame: at enrollment

    evaluation of inhibitory control for all subjects except control cases

  16. REY'S 15-WORD TEST

    Time frame: at enrollment

    evaluation of long term memory for all subjects except control cases

  17. REY OSTERRIETH COMPLEX FIGURE

    Time frame: at enrollment

    evaluation of visuospatial skills for all subjects except control cases

  18. FACE TEST

    Time frame: at enrollment

    evaluation of ability to recognize mental states of others for all subjects except control cases

  19. NEUROPSYCHIATRICH INVENTORY (NPI)

    Time frame: at enrollment

    interview assessing behavioral of others for all subjects except control cases

  20. FRONTAL ASSESSMENT BATTERY (FAB)

    Time frame: at enrollment

    evaluation of executive functions; for all subjects except control cases

  21. MINIMENTAL STATE EXAMINATION (MMSE)

    Time frame: at enrollment

    cognitive screening only for subjects with ADD and with Mild Cognitive Impairment (MCI)

Sponsors and collaborators

Lead sponsor

Fondazione Don Carlo Gnocchi ETS

Other

Collaborators

  • University of Cagliari

Registry information

Acronym: SANDY

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Mar 13, 2025
Registry last updated
Mar 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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