LONgitudinal and Integrated Evaluation of Biomarkers in reLation to phenotYpe in ALS

NCT07312240 | Recruiting

• 1 other identifier: 23A307
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons, leading to paralysis and death. Despite its uniformly fatal outcome, ALS shows marked clinical heterogeneity with respect to phenotype, progression rate, cognitive involvement, and survival. This heterogeneity limits prognostic accuracy and complicates patient stratification in both clinical practice and research settings. Neurochemical biomarkers have emerged as promising tools to improve diagnosis, prognostication, and understanding of ALS pathophysiology. Among them, neurofilament light chain (NfL) represents the most established biomarker, reflecting axonal degeneration. Additional biomarkers, including glial fibrillary acidic protein (GFAP), phosphorylated tau (p-tau181), and Alzheimer's disease-related markers (Aβ42 and Aβ40), may provide complementary information regarding astroglial activation, motor neuron subtype involvement, and cognitive-behavioral features. However, the phenotypic correlates, longitudinal trajectories, and biological determinants of these biomarkers in ALS are not yet fully understood. The LONELYALS study is an ongoing, monocentric, observational cohort study with a case-control component, designed to investigate the relationships between ALS phenotype and a comprehensive panel of cerebrospinal fluid (CSF) and blood biomarkers. The study will enroll 140 adult patients with ALS and collect longitudinal clinical, neuropsychological, biological, and laboratory data over a follow-up period of up to 36 months. By integrating biomarker measurements with detailed phenotypic characterization, the study aims to clarify biomarker origins, determinants, and prognostic value, and to identify novel CSF biomarkers relevant to ALS.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Phenotyping; Biomarker

Outcome Measures

Primary Outcomes (11)

• Clinical - ALSFRS-R score

  At enrolment, at 6 months, at 12 months

• Clinical - Penn UMN Score

  At enrolment, at 6 months, at 12 months

• Clinical - LMN score

  At enrolment, at 6 months, at 12 months

• Neuropsychological phenotyping

  Score at Montreal Cognitive Assessment

  At enrollment

• Neurophysiological - Limb denervation score (EMG)

  At enrollment

• Neurophysiological - CMCT (central motor conduction time) (TMS, transcranial magnetic stimulation)

  At enrolment

• Arterial blood gas analysis - PaO2

  At enrollment

• Arterial blood gas analysis - PaCO2

  At enrolment

• Neuroradiological phenotyping

  Presence or absence of T2-FLAIR hyperintensity of the corticospinal tracts

  At enrollment

• Neurochemical - Plasma NFL

  An enrolment, at 6 months, at 12 months

• Outcome measure for controls

  Exclusion of ALS or other neurodegenerative diseases

  At enrolment

Study Arms (2)

ALS Patients

OTHER

Patients with Amyotrophic Lateral Sclerosis

Diagnostic Test: Lumbar Puncture for analysis of Cerebrospinal Fluid; Diagnostic Test: Deep Phenotyping; Diagnostic Test: Routine blood chemistry analysis and genetic analysis

Controls

OTHER

Individuals undergoing Lumbar Puncture for neurological symptoms but finally having no evidence of nervous system pathology

Diagnostic Test: Lumbar Puncture for analysis of Cerebrospinal Fluid

Interventions

Lumbar Puncture for analysis of Cerebrospinal Fluid DIAGNOSTIC_TEST

Lumbar Puncture for analysis of Cerebrospinal Fluid for subsequent discovery and validation of a novel biomarker

ALS Patients; Controls

Deep Phenotyping DIAGNOSTIC_TEST

Clinical, neurophysiological, neuroradiological, neuropsychological phenotyping and respiratory investigation

ALS Patients

Routine blood chemistry analysis and genetic analysis DIAGNOSTIC_TEST

Plasma sampling and genetic analysis

ALS Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of Amyotrophic Lateral Sclerosis (ALS);
• age ≥18 y;
• feasibility of lumbar puncture (LP);
• informed consent.

You may not qualify if:

• severe medical comorbidities;
• recent traumatic, inflammatory, vascular, or neoplastic Central Nervous System disease; contraindications to LP.
• age ≥18 y;
• individuals undergoing LP for neurological symptoms;
• no evidence of nervous system pathology;
• informed consent.

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead

Study Sites (1)

Istituto Auxologico Italiano IRCCS

Milan, Lombardy, 20149, Italy

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Spinal Puncture; Genetic Testing

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Central Study Contacts

Federico Verde, MD

CONTACT

+3902619111; f.verde@auxologico.it

Luca Grappiolo, Dr.

CONTACT

+3902619111; luca.grappiolo@auxologico.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: December 31, 2025
• Study Start: April 17, 2025
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 15, 2027
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

IT (1)