Motor Neuron Disease, Amyotrophic Lateral SclerosisNCT06320444
Non-invasive Spinal, Cortical, and Sensorimotor Biomarkers in Motor Neurone Disease
An observational study of Motor Neuron Disease, Amyotrophic Lateral Sclerosis and Motor Neuron Disease Progressive Spinal Muscle Atrophy, run by University of Dublin, Trinity College at 1 site in Ireland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis, Motor Neuron Disease Progressive Spinal Muscle Atrophy, Primary Lateral Sclerosis
- What is being tested?
- 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)
- Type of treatment
- Surgery or procedure
- How many people
- 240 participants
- Where
- 1 siteIreland
- Study dates
- 15 Jun 2023to 15 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy controls and patients diagnosed with ALS, MS, PLS, PMA, and SMA.
Who may be able to join
- -
- 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.
Who cannot join
- -
- 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:
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Ireland1 site, 1 recruiting
- Recruiting
Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
Dublin, Leinster, Dublin 2
Orla Hardiman,, BSc MB BCh BAO MD FRCPI FAAN, +353 1 896 4497, hardimao@tcd.ie
Prabhav Mehra, BE MSc, +3530894781347, mehrap@tcd.ie
About this study
Official title: Developing Novel Non-invasive Electrophysiological Biomarkers of Dysfunction in Spinal and Cortical Pathways and Sensorimotor Impairments in Motor Neurone Disease
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.
Read the detailed description
Background:
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 its unique alignment in the 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.
Aim:
To develop, test, and employ non-invasive techniques to explore (dys)function between motor, sensory brain, and spinal networks in ALS. The project will address if the electrical activity of the cortical-spinal network by the of use peripheral stimulation (vibration, electrical nerve stimulation) to probe and reveal the normal or abnormal communication between brain and spinal networks. It is expected to reveal novel neurophysiological signatures in ALS patients compared to healthy controls.
Study Design \& Data Analysis:
Surface electrodes will be mounted over the targeted regions in conjunction with High-Density EEG and High-density Electromyography (EMG). A physical and mathematical model of the underlying sources of electric activity (source localization) will be carried out at rest, during task, and with non-invasive peripheral nerve stimulation (PNS) and TMS. A separate paradigm will augment sensorimotor communication between the primary motor cortex (M1) and the somatosensory cortex (S1). Mild vibration (5N/< 500 grams) will be applied to the wrist and/or bicep tendon transcutaneously. Vibration in conjunction with non-invasive peripheral nerve stimulation will induce transient changes (30 seconds maximum) in the intrinsic excitability of motor neurons in the spinal cord. Surface EMG will capture altered MN activity at the spinal level and the anticipated augmented communication in cortical networks (S1-M1) will be captured with EEG through connectivity analysis. Non-invasive transcranial magnetic stimulation in conjunction with vibration/nerve stimulation will be recorded to explore upper motor neurone influences on the altered intrinsic excitability of spinal motor neurons.
Data collection:
EXG-EEG-EMG and TMS/Peripheral Stimulation recordings will be conducted using a BioSemi® ActiveTwo system with 128 active sintered Ag-AgCl electrodes and headcaps (BioSemi B.V., Amsterdam, The Netherlands). The TMS system is a Brainbox DuoMAG (Brainbox Ltd., Cardif, Wales, UK) which can be used with a Digitimer peripheral stimulator.
- Conditions
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis, Motor Neuron Disease Progressive Spinal Muscle Atrophy, Primary Lateral Sclerosis, Multiple Sclerosis, Postpoliomyelitis Syndrome
- Being tested
- 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)
- Keywords
- Electroencephalography (EEG), Peripheral Nerve Stimulation, Vibration-Induced Stimulation, Neurodegeneration, Electrophysiology, Biomarkers, Neuromuscular Physiology, Spinal Connectivity
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Multiple Sclerosis, Postpoliomyelitis Syndrome, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)Procedure or surgery
Also called Peripheral Nerve Stimulation, Vibration Induced Stimulation
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)
| Study group | Role | What they receive |
|---|---|---|
| Controls | Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis Receives: Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) | |
| Amyotrophic lateral sclerosis Patients | Not described Receives: Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) | |
| Multiple Sclerosis patients | Not described Receives: Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) | |
| Postpoliomyelitis syndrome patients | Not described Receives: Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) | |
| Muscular Atrophy patients | Not described Receives: Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start15 Jun 2023
- Primary completion15 Dec 2024 (estimated)
- Study completion15 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Motor Neuron Disease, Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Dublin, Trinity College
- Sponsor type
- University, hospital or other
- Collaborators
- Motor Neurone Disease Association, UK, Irish Research Council, Health Research Board, IE, Research Motor Neurone, IE, Thierry Latran Foundation, FR, ALS Association, USA
- Responsible party
- Principal investigator, Orla Hardiman, University of Dublin, Trinity College
- Investigators
- Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN, Principal investigator, Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06320444
- Sponsor's protocol ID
- CRFSJ0297
- Status last verified
- Mar 2024
- First submitted
- 19 Dec 2022
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Raw data from this study may be made available in anonymized form upon request from qualified investigators subject to the approval by the Data Protection Office (DPO) and Office of Corporate Partnership and Knowledge Exchanges (OCPKE) in Trinity College Dublin, the University of Dublin.
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing Novel Non-invasive Electrophysiological Biomarkers of Dysfunction in Spinal and Cortical Pathways and Sensorimotor Impairments in Motor Neurone Disease
- ClinicalTrials.gov ID
- NCT06320444
- Acronym / sponsor ID
- CRFSJ0297
- 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
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- University of Dublin, Trinity CollegeUniversity, hospital or other
- Collaborators
- Motor Neurone Disease Association, UK, Irish Research Council, Health Research Board, IE, Research Motor Neurone, IE, Thierry Latran Foundation, FR, ALS Association, USA
- Study start
- 15 Jun 2023 (actual)
- Primary completion
- 15 Dec 2024 (estimated)
- Study completion
- 15 Jul 2025 (estimated)
- First posted
- 20 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
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 its unique alignment in the 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.
Aim:
To develop, test, and employ non-invasive techniques to explore (dys)function between motor, sensory brain, and spinal networks in ALS. The project will address if the electrical activity of the cortical-spinal network by the of use peripheral stimulation (vibration, electrical nerve stimulation) to probe and reveal the normal or abnormal communication between brain and spinal networks. It is expected to reveal novel neurophysiological signatures in ALS patients compared to healthy controls.
Study Design \& Data Analysis:
Surface electrodes will be mounted over the targeted regions in conjunction with High-Density EEG and High-density Electromyography (EMG). A physical and mathematical model of the underlying sources of electric activity (source localization) will be carried out at rest, during task, and with non-invasive peripheral nerve stimulation (PNS) and TMS. A separate paradigm will augment sensorimotor communication between the primary motor cortex (M1) and the somatosensory cortex (S1). Mild vibration (5N/< 500 grams) will be applied to the wrist and/or bicep tendon transcutaneously. Vibration in conjunction with non-invasive peripheral nerve stimulation will induce transient changes (30 seconds maximum) in the intrinsic excitability of motor neurons in the spinal cord. Surface EMG will capture altered MN activity at the spinal level and the anticipated augmented communication in cortical networks (S1-M1) will be captured with EEG through connectivity analysis. Non-invasive transcranial magnetic stimulation in conjunction with vibration/nerve stimulation will be recorded to explore upper motor neurone influences on the altered intrinsic excitability of spinal motor neurons.
Data collection:
EXG-EEG-EMG and TMS/Peripheral Stimulation recordings will be conducted using a BioSemi® ActiveTwo system with 128 active sintered Ag-AgCl electrodes and headcaps (BioSemi B.V., Amsterdam, The Netherlands). The TMS system is a Brainbox DuoMAG (Brainbox Ltd., Cardif, Wales, UK) which can be used with a Digitimer peripheral stimulator.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Controls | – | Procedure: 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis |
| 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy controls and patients diagnosed with ALS, MS, PLS, PMA, and SMA.
Key inclusion criteria (7 listed)
- -
- age and gender matched to patient groups
- intact physical ability to take part in the experiment.
- Diagnosis of ALS, PLS, PMA, SMA, Polio or MS
- capable of providing informed consent.
Key exclusion criteria (9 listed)
- -
- History of neuromuscular
- neurological or active psychiatric disease disease
- history of reaction or allergy to recording environments, equipment and the recording gels.
- presence of active psychiatric disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG)Also: Peripheral Nerve Stimulation, Vibration Induced StimulationNoninvasive 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) | Procedure or surgery | Amyotrophic lateral sclerosis Patients, Controls, Multiple Sclerosis patients, Muscular Atrophy patients, Postpoliomyelitis syndrome patients |
Primary outcome
Biomarker of sensorimotor integration
Time frame: Baseline to 2-years after baseline
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.
Determination of the feasibility of sensorimotor signatures as reliable biomarkers of ALS
Time frame: Baseline
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.
Non-invasive recording of the SC functional neuro-electric activity
Time frame: Baseline
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Individual participant dataSharing planned: Yes. Raw data from this study may be made available in anonymized form upon request from qualified investigators subject to the approval by the Data Protection Office (DPO) and Office of Corporate Partnership and Knowledge Exchanges (OCPKE) in Trinity College Dublin, the University of Dublin.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN principal investigator
Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Motor Neuron Disease, Amyotrophic Lateral Sclerosis and Motor Neuron Disease Progressive Spinal Muscle Atrophy, run by University of Dublin, Trinity College at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN (+353 1 896 4497, hardimao@tcd.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker of sensorimotor integration (time frame: Baseline to 2-years after baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024; AzTrials last refreshed its copy on 7 Nov 2026.