Non-invasive Spinal, Cortical, and Sensorimotor Biomarkers in Motor Neurone Disease

NCT06320444 | Recruiting DMC

• 1 other identifier: CRFSJ0297
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Substantial variability exists in the onset, and rate of degeneration across individuals with Motor Neurone Disease (MND) or Amyotrophic Lateral Sclerosis (ALS). This variability requires biomarkers that accurately classify and reliably track clinical subtypes as the disease progresses. Degeneration occurs in the brain and spinal cord, however, non-invasive diagnosis of spinal cord function remains highly challenging due to its unique alignment in spine. Disruption of complex spinal and cortical circuits that transmit and process neural signals for position sense and movement has not been adequately captured in the neurophysiological profiling of ALS patients. The overarching aim of this study is to reveal and quantify the extent of change in the sensorimotor integration and its potential contribution to network disruption in ALS.

Conditions

Motor Neuron Disease, Amyotrophic Lateral Sclerosis; Motor Neuron Disease Progressive Spinal Muscle Atrophy; Primary Lateral Sclerosis; Multiple Sclerosis; Postpoliomyelitis Syndrome

Keywords

Electroencephalography (EEG); Peripheral Nerve Stimulation; Vibration-Induced Stimulation; Neurodegeneration; Electrophysiology; Biomarkers; Neuromuscular Physiology; Spinal Connectivity

Outcome Measures

Primary Outcomes (3)

• Biomarker of sensorimotor integration

  A viable biomarker of sensorimotor integration for reliable and early distinction between healthy people and Motor Neuron Disease patient sub-phenotypes. This will be achieved by comparing connectivity measures between EEG, Non-cortical CNS, and EMG electrophysiological signals. The integration will also be seen in spectral analysis measures.

  Baseline to 2-years after baseline

• Determination of the feasibility of sensorimotor signatures as reliable biomarkers of ALS

  The sensorimotor integration and signature biomarkers achieved during outcome 1 will be correlated with the clinical scores and will be statistically tested for reliability and robustness. The effect sizes of these statistical and correlation matrices will be used to evaluate the feasibility of the signatures as reliable biomarkers for motor neuron conditions like ALS.

  Baseline

• Non-invasive recording of the SC functional neuro-electric activity

  Understanding the role of spinal cord (SC) in neuromuscular physiology (in both impaired and healthy individuals) and will also assist in discovering biomarkers in Brain-SC Peripheral connections. This is a perspective outcome that will be future based upon the inferences gained by the first two outcomes.

  Baseline

Study Arms (5)

Controls

Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis

Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)

Amyotrophic lateral sclerosis Patients

Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)

Multiple Sclerosis patients

Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)

Postpoliomyelitis syndrome patients

Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)

Muscular Atrophy patients

Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)

Interventions

232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) PROCEDURE

Noninvasive 232 Channel Electrode Electrophysiological signals (EEG-ECG-EMG-EXG) will be recorded from electrodes placed in a montage over the scalp, neck,and upper back along with muscles located on the hand. These signals will be recorded while resting or performing voluntary task. Other Intervention: The 232 electrode noninvasive electrophysiological data will be recorded in response to non-invasive peripheral nerve stimulation or vibration induced stimulation. These sessions are designed to engage specific cortical motor networks of interest for evaluating sensorimotor networks. (Cognitive, behavioural, motor, spinal, and sensory)

Also known as: Peripheral Nerve Stimulation, Vibration Induced Stimulation

Amyotrophic lateral sclerosis Patients; Controls; Multiple Sclerosis patients; Muscular Atrophy patients; Postpoliomyelitis syndrome patients

Eligibility Criteria

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

Study Population

Healthy controls and patients diagnosed with ALS, MS, PLS, PMA, and SMA.

You may qualify if:

• Healthy Volunteers:
• age and gender matched to patient groups
• intact physical ability to take part in the experiment.
• Patients:
• Diagnosis of ALS, PLS, PMA, SMA, Polio or MS
• capable of providing informed consent.

You may not qualify if:

• Healthy Controls:
• History of neuromuscular
• neurological or active psychiatric disease disease
• history of reaction or allergy to recording environments, equipment and the recording gels.
• Patients:
• presence of active psychiatric disease
• any medical condition associated with severe neuropathy (e.g. poorly controlled diabetes).
• History of reaction or allergy to recording environments, equipment and the recording gels.

Sponsors & Collaborators

• University of Dublin, Trinity College: lead
• Motor Neurone Disease Association, UK: collaborator
• Irish Research Council, IE: collaborator
• Health Research Board, IE: collaborator
• Research Motor Neurone, IE: collaborator
• Thierry Latran Foundation, FR: collaborator
• ALS Association, USA: collaborator

Study Sites (1)

Academic Unit of Neurology, Trinity College Dublin, The University of Dublin

Dublin, Leinster, Dublin 2, Ireland

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Multiple Sclerosis; Postpoliomyelitis Syndrome; Nerve Degeneration

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Poliomyelitis; Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuroinflammatory Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN

  Academic Unit of Neurology, Trinity College Dublin, The University of Dublin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN

CONTACT

+353 1 896 4497; hardimao@tcd.ie

Prabhav Mehra, B.E. MSc.

CONTACT

+353 0894781347; mehrap@tcd.ie

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: March 20, 2024
• Study Start: June 15, 2023
• Primary Completion: December 15, 2024
• Study Completion: July 15, 2025
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Due to ethical constraints and the time required for data quality checks, data will only be made available in fully anonymised format following the publication of results.

Locations

IE (1)