A Muscle-brain Interplay Study in Neurological Disorders

NCT07477821 | Recruiting

• 1 other identifier: PNRR-MCNT1-2023 12378447
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 4

Brief Summary

Despite the improvements in life expectancy, neurodegenerative diseases (NDGs) have become the most dreaded disorders of older people. Aged brains show characteristic changes that are linked to neurodegeneration raising the question of whether these hallmarks represent the harbingers of NDGs. Lifestyle factors including, in particular physical exercise, have given particular attention to factors associated to movement issue as ones of the major factors in modulating the risk of developing NDGs, emphasizing the interest in the muscle-brain axis. Indeed, one of the crucial systems severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, and the neuromuscular junction (NMJ) represents the critical region at the level of which the two entities communicate. Even if controversy exists on whether pathological events beginning at the NMJ precede or follow loss of motor units, some recent data highlight as NGDs (e.g. Amyotrophic Lateral Sclerosis, Alzheimer's Disease, and Parkinson's Disease) and Aging share some common pathologic features such as the loss of fast-twich fiber, a decreased number of synaptic vesicles and sarcopenia giving evidence supports the notion that NMJ dismantlement can occur independently from motor neuron degeneration and may represent an early pathogenic signature of muscle-nerve communication defects. The M-Brain project is an observational, analytical case-control study that will apply a new approach to interpret data underling the NMJ dismantlement in NDGs patients by comparing their clinical and biological information with data obtained from people who have had a so called "good aging" and those who have had a "bad aging". The study will collect data useful to identify potential predisposing or risk factors for the subsequent development of a NDGs or able to predict the phenotype traiectories of selected pathologies with differerent movement levels. The combination of a muscular and neurological phenotyping and a biological characterization combining biomarkers, miRNA and extracellular vesicle (EV) assessments will allow to better identify the determinants of muscle-brain cross-talk that can then be used as potential indicators for the definition of critical morphological and functional components involved in aging and some NGDs. The project then will aim to identify phenotyope trajectories of patients giving particular attention to the brain-muscle axis and movement issues in order to provide information useful for future clinical strategies able to minimaze risk/predisponent Factors.

Conditions

Neurological Disorders; Health Adult Subjects

Keywords

muscle; brain; aging; Neuromuscolar

Outcome Measures

Primary Outcomes (1)

• Change from baseline in The Edmonton Frail Scale (EFS)

  The EFS is one of just a few frailty assessment tools that capture multidimensional aspects of frailty. The EFS is used to flag more specific issues that warrant closer attention and follow up. In this way, healthcare providers can use frailty information to create an individualized care plan to be discussed with the person who has been assessed.

  At baseline and T1 (6 months)

Study Arms (2)

Bad Aging Group

This group include: 1. No-neurodegenerative disease group (No-NDG) that will comprehend: (i) subjects with an age older than 60 years and with or without sarcopenia and/or neurological impairment (such as mild cognitive impairments or extrapyramidal signs) and (ii) Patients (pts) with Severe Acquired Brain Injury (sABI) that are characterised by sarcopenia and cognitive impairment 2. The Neurodegenerative disease group (NDG) that will comprehend: ALS with or without cognitive impairments/sarcopenia; Alzheimer Disease (AD) with or without sarcopenia and Parkinson Disease (PD) with or without sarcopenia

Good Aging Group

This group will include subjects aged more than 60 years and without muscular (e.g. sarcopenia) and/or neurological (e.g. cognitive) impairment

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients to be enrolled in the study will be those admitted at the hospitals involved in the project. Healthy volunteers may be recruited among patients' relatives or among hospital staff who are not involved in the study.

You may qualify if:

• for Good aging group:
• Subjects aged 60 years or older
• Frailty Index below the pathological cut-off (\>0.25)
• Absence of general cognitive impairment (MMSE \> 24 points)
• Absence of a diagnosis of sarcopenia
• for Bad aging group:
• Patients aged over 60 years
• Exclusive presence of one of the following diagnoses:
• Definite, probable, or probable laboratory-supported Amyotrophic Lateral Sclerosis (ALS), either sporadic or familial, according to the revised El Escorial Criteria for ALS diagnosis.
• Parkinson's disease (PD) according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease (Postuma et al., Mov Disord., 2015 Oct; 30(12): 1591-1601).
• Alzheimer's disease (AD), possible or probable, according to international diagnostic guidelines.
• Diagnosis of severe acquired brain injury according to the Italian Guidelines for the Care of Patients in Vegetative State and Minimally Conscious State 2011 (approved by the Unified Conference on May 5, 2011 - Ministry of Health, Italy), with the presence of Sarcopenia.
• Presence of Mild Cognitive Impairment (MCI), subjective memory complaint, or deficit in a single cognitive domain, according to international criteria and in absence of established neurological diseases and sarcopenia.
• Presence of Sarcopenia as defined by the EWGSOP2 Sarcopenia Consensus, in the absence of cognitive deficits and established neurological diseases.

You may not qualify if:

• Inability to provide informed consent.
• Presence of severe and/or acute comorbidities (e.g., uncontrolled diabetes, heart failure, or a diagnosis of oncological disease), as determined by the research team.
• Evidence of other previous neurological or psychiatric disorders involving the cognitive domain.
• Uncontrolled or complicated systemic diseases or history of traumatic brain injury.
• For subjects with Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS), individuals with a history of epilepsy will also be excluded.

Sponsors & Collaborators

• Istituti Clinici Scientifici Maugeri SpA: lead
• University of Roma La Sapienza: collaborator
• Universita degli Studi di Catania: collaborator
• IRCCS Centro Neurolesi Bonino Pulejo: collaborator

Study Sites (4)

Universita degli Studi di Catania

Catania, 95131, Italy

ACTIVE NOT RECRUITING

IRCCS Centro Neurolesi Bonino Pulejo

Messina, 98123, Italy

RECRUITING

Istituti Clinici Scientifici Maugeri IRCCS, Milan Institute

Milan, 20138, Italy

RECRUITING

University of Roma La Sapienza

Roma, 00185, Italy

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Nervous System Diseases

Central Study Contacts

Christian Lunetta, MD

CONTACT

+39 0250725266; christian.lunetta@icsmaugeri.it

Davide Sattin, PsyD, PhD

CONTACT

+390250725246; davide.sattin@icsmaugeri.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: March 17, 2026
• Study Start: July 24, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

IT (4)