The Aim of the Study is to Characterize Patients Exhibiting Muscular Atrophy and Weakness Who Require a Muscle Biopsy for Diagnosis (IBM vs Atypical MND), Through an Innovative Technique Which Enables the Evaluation of the Neuromuscular Junction Involvement in Each Condition (TDP-signatures)

August 26, 2026 updated by: Stefano Previtali, IRCCS San Raffaele

Comparative Analysis of TDP-43 Pathology in Skeletal Muscle Biopsies With Electrostimulation for Enhanced Neuromuscular Junction Sampling in Patients Affected by Inclusion Body Myopathy (IBM) and Motor Neuron Disease (MND)

The aim of the study is to characterize 30 patients exhibiting muscular atrophy and weakness who require a muscle biopsy for diagnosis (suspected inclusion body myopathy vs atypical motor neuron disease), through an innovative technique (a muscle biopsy with Electrostimulation for Enhanced Neuromuscular Junction sampling), to evaluate the involvement of the neuromuscular junction in each disease and to better characterize shared and divergent patterns of TDP-43 pathology within the peripheral nervous system in both disorders.

Study Overview

Status

Active, not recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Italy
- - Milan, Italy
    - IRCCS Ospedale San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

30 adult patients with a neuromuscular disorder (suspected IBM or in differential diagnosis between IBM and MND)

Description

Inclusion Criteria:

Patients exhibiting progressive muscle weakness and atrophy with a classic clinical IBM pattern or with an atypical clinical IBM pattern or with an atypical MND pattern
Able to understand and sign the informed consent
Treated according to standard of care clinical practice

Exclusion Criteria:

Contraindications to needle EMG or skeletal muscle biopsy
Psychiatric diseases that may interfere with adherence to the follow-up protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Motor Neuron Disease
Inclusion body myopathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic sensitivity of an integrated clinical, neurophysiological, metabolic and histopathological model in the differential diagnosis between IBM and MND. Time Frame: At the end of the follow-up period (24 months of follow-up)	To achieve a diagnostic sensitivity of >90% for the differential diagnosis between IBM and MND integrating clinical variables (site of onset, scales reflecting disease progression rate, muscle strength), neurophysiological indices (presence and degree of active denervation signs, presence of myopathic or neurogenic motor unit potentials), histopathological parameters (myopathic or neuropathic pattern of disease) and metabolic measures (hyper- vs hypo-metabolism) into a multivariable binary logistic regression model, using the final diagnosis confirmed during longitudinal follow-up as the reference standard.	At the end of the follow-up period (24 months of follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate signs of muscle and neuromuscular junction (NMJ) involvement at neuropathological level in each disease Time Frame: At the end of the follow-up period (24 months of follow-up)	To investigate disease-specific histological signatures, comparing the pattern of fiber degeneration, the presence of inflammatory infiltrates, the presence of protein aggregation markers (such as pTDP-43) and their localization, the presence of mitochondrial changes (the percentage of age-exceeding number of COX-negative fibers) and the NMJ involvement by evaluating the presynaptic and postsynaptic integrity (quantified as the percentage of synaptophysin and Ach-R clustering, respectively) between IBM and MND (through Fisher's exact test or Mann-Whitney U test, as appropriate) and to evaluate the prognostic role of each histological parameter (through Kaplan-Meier followed by log-rank test and Cox proportional hazards regression).	At the end of the follow-up period (24 months of follow-up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2026

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2030

Study Registration Dates

First Submitted

August 20, 2026

First Submitted That Met QC Criteria

August 26, 2026

First Posted (Actual)

September 1, 2026

Study Record Updates

Last Update Posted (Actual)