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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Deep Phenotyping: Clinical, neurophysiological, neuroradiological, neuropsychological phenotyping and respiratory investigation

Routine blood chemistry analysis and genetic analysis: Plasma sampling and genetic analysis

Study 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.

Eligibility

Primary outcome measure(s)

• 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 — At enrollment
  Score at Montreal Cognitive Assessment
• 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 — At enrollment
  Presence or absence of T2-FLAIR hyperintensity of the corticospinal tracts
• Neurochemical - Plasma NFL — An enrolment, at 6 months, at 12 months
• Outcome measure for controls — At enrolment
  Exclusion of ALS or other neurodegenerative diseases

Trial sites (1)

More Istituto Auxologico Italiano trials in Italy

Other trials for the same condition