Brief Summary

BACKGROUND/RATIONALE: The paucity of biomarkers for the diagnosis and monitoring of patients affected by Amyotrophic Lateral Sclerosis (ALS) is one of the greatest concerns in ALS clinics and research. Phenotypic signs, electrophysiological test and clinical scales are currently used for ALS diagnosis and follow up before and after treatments. Nowadays, the diagnosis and differential diagnosis used to discriminate ALS from other comparable neurodegenerative diseases, are time-consuming and complex processes that reduce the time for a prompt intervention. Thus, the scientific community is asked to strive for new, measurable, fast and objective biomarkers for the diagnosis and stratification of patients. Saliva is a complex biofluid composed of bioactive molecules that can be collected by means of a non-invasive procedure. The possibility to simultaneously monitor all the variations in the endocrine, electrolytic and metabolic messengers in saliva has recently suggested its use for the diagnosis of complex diseases, like neurodegenerative diseases, but only limited information are available on the potential of saliva as alternative carrier of ALS biomarkers. OBJECTIVES: The aim of the present project is to optimize an innovative, non-invasive and fast procedure for the ALS onset and for the stratification of ALS patients, taking advantage of the sensitivity of Raman Spectroscopy (RS) and of accessible saliva. Fondazione Don Gnocchi (FDG) preliminary results on a small cohort of subjects demonstrated the feasibility of the methodology and the ability of LABION protocol to obtain a reproducible Raman fingerprint of saliva that can be used for the discrimination of healthy subjects, ALS patients and subjects affected by other types of neurological diseases. METHODS: Starting from FDG preliminary results, the biochemical composition of saliva in patients with diagnosed ALS will be evaluated and statistically compared with the one obtained from age and sex-matched healthy subjects and from patients affected by other neurological diseases (Parkinson's and Alzheimer's diseases). Moreover, an intra-group ALS clustering will be analysed in order to verify a different Raman fingerprint obtained from ALS patients with a bulbar or spinal onset. The collected Raman data will be processed using a multivariate analysis approach through Principal Component Analysis - Linear Discriminant Analysis (PCA-LDA). The classification model will be created using cross-validation and subset validation. Thanks to RS, the overall composition of saliva will be established with minimal sample preparation, providing comprehensive biochemical fingerprint of the sample. In parallel, routine salivary parameters will be measured including viscosity, pH, total protein and carbohydrates concentration, amylase and pepsin, cortisol and Chromogranin A. EXPECTED RESULTS: By the end of this study, the investigators expected to verify the possibility to use the Raman salivary pattern as new promising biomarker for ALS diagnosis and progression to be related with clinical scales for the personalized and fine tuning of the therapeutic approach. The intent of this project is to create a classification model able to:

1.Determine the ALS onset
2.Discriminate the signal obtained from ALS patients from the one collected from other neurodegenerative diseases
3.Stratify ALS patients into bulbar and spinal onset
4.Correlate the Raman data with clinical and paraclinical scales used nowadays for ALS diagnosis and monitoring

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

126

participants targeted

Target at P50-P75 for all trials

Timeline

Completed

Started Jul 2019

Longer than P75 for all trials

Geographic Reach

1 country

2 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.5 years study duration

Study Start

First participant enrolled

July 1, 2019

Completed

7 months until next milestone

First Submitted

Initial submission to the registry

January 15, 2020

Completed

3 days until next milestone

First Posted

Study publicly available on registry

January 18, 2020

Completed

3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2023

Completed

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed

Last Updated

February 4, 2025

Status Verified

January 1, 2024

Enrollment Period

4.3 years

First QC Date

January 15, 2020

Last Update Submit

January 31, 2025

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Raman SpectroscopyAmyotrophic Lateral SclerosisBiomarkerDiagnosis

Outcome Measures

Primary Outcomes (4)

Identification of a new ALS biomarker in the saliva of people affected by Amyotrophic Lateral Sclerosis (ALS) using Raman Spectroscopy
Raman spectroscopy will be used to identify a new salivary biomarker for the fast discrimination between healthy subjects and patients affected by ALS. Saliva samples will be collected and processed without any labeling procedure, investigating the overall salivary biochemistry of the two investigated groups. Using multivariate analysis on the collected data we will be able to create a classification model that can discriminate ALS signature from healthy subjects.
One day
Evaluation of the spectral differences in the saliva of patients with different neurological diseases
The Raman data collected from ALS patients will be compared with the one obtained from patients affected by Alzheimer's and Parkinson's disease, validating our methodology as differential diagnostic tool for the discrimination of ALS from other neurological diseases
One day
Evaluation of the spectral differences in the saliva of patients with bulbar or spinal ALS onset
The intra-group analysis of recruited spinal and bulbar ALS patients will reveal the Raman fingerprint associated to the specific pathological subtype. This result will be important for the stratification of ALS patients after the ALS diagnosis.
One Day
Correlation of Raman data with clinical and paraclinical data
Raman data related to the ALS group will be correlated with clinical and paraclinical data, validating in this way our methodology. Collected data will be correlated primarily with factors that can alterate the biochemical composition of saliva including age, smoking habit, time before the last meal, time before teeth brushing, percutaneous endoscopic gastrostomy, mechanical ventilation and others. Consequently the same data will be analysed finding correlations with ALS-FRS (Amyotrophic Lateral Sclerosis - Functional Rating Scale), WHO-QOL (World of Health Organization - Quality of Life), blood analysis outcome, time from the diagnosis and other
One Day

Study Arms (5)

Healthy Subjects

20 Healthy subjects in a good state of health comparable by age and sex with the other selected groups