ALS (Amyotrophic Lateral Sclerosis)MotorMarkerNCT05663008
Impairments of Neuro-muscular Communication in Motor-Neuron Disease: A Bio-Marker for Early and Personalised Diagnosis
An observational study of ALS (Amyotrophic Lateral Sclerosis) and Postpoliomyelitis Syndrome, run by University of Dublin, Trinity College at 1 site in Ireland.
Trial summary
Motor neuron disease (MND) or ALS is a nervous system disease. ALS leads to a loss of movement ability that eventually leads to death. At the moment, there is no known treatment for ALS. Early diagnosis in individuals improves clinical care and facilitates timely entry into clinical trials. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- ALS (Amyotrophic Lateral Sclerosis), Postpoliomyelitis Syndrome, Spinal Muscular Atrophy
- What is being tested?
- 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)
- Type of treatment
- Surgery or procedure
- How many people
- 400 participants
- Where
- 1 siteIreland
- Study dates
- 1 Oct 2015to 30 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: MND (ALS, PLS, PMA, SMA, Polio or MS) patients will be recruited from the national MND/ALS register, an ongoing registry run in conjunction with Beaumont Hospital ALS clinic, run by Professor Orla Hardiman. Healthy controls will be recruited from the student population and age-matched controls from the general public, as well as a dataset of pre-consented healthy volunteers which is maintained at the Academic Unit of Neurology, Trinity College Dublin.
Who may be able to join
- Healthy Volunteers:
- age and gender-matched to patient groups
- the 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:
- the 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. Contact the study team or a site near you to ask about taking part.
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
Saroj Bista, MSc, +353 89 945 8246, sbista@tcd.ie
About this study
Motor neuron disease (MND) or ALS is a nervous system disease. ALS leads to a loss of movement ability that eventually leads to death. At the moment, there is no known treatment for ALS. Early diagnosis in individuals improves clinical care and facilitates timely entry into clinical trials. However, current methods for diagnosis are primarily clinical, and to date, no cost-effective biomarkers have been developed. Our objective is to identify a robust non-invasive neurophysiological-based system that can be used both as a biomarker of disease onset, and a measurement of progression using quantitative EEG and surface EMG (bipolar and high-density).
The investigators postulate that analysing the joint recordings of EEG and EMG (bipolar or high-density) can give measures that better distinguish healthy people and ALS patient subgroups and that the findings can be developed as biomarkers of early diagnosis and disease progression.
Read the detailed description
Amyotrophic Laterals Sclerosis (ALS) or Motor Neuron Disease (MND) is a terminal neurodegenerative disease, that leads to progressive loss of motor function. Treatment of ALS remains an unresolved challenge and despite intensive research, diagnosis and therapy are not yet adequately personalised . New therapeutics and the quality of care after diagnosis can be enhanced by early diagnosis at the individual patient level, enabling tailored care and individualised treatment.
To personalise the diagnosis, there is a need for reliable quantitative biomarkers, for early detection of disease onset and to distinguish the different sub-types of the disease. Specifically, several biomarkers have been investigated for use in ALS, including Motor Unit Number Estimation (MUNE), Motor Unit Number Index (MUNIX), Cortical Excitability in Transcranial Magnetic Stimulation (TMS), EMG Inter-muscular Coherence, Magnetic Resonance (MR) and other imaging techniques, and EEG signatures. However, the diagnostic utility of these techniques, especially the inexpensive non-invasive recordings of electrical muscle activity - bipolar or high-density surface electromyography (sEMG), and electrical brain activity -surface electroencephalography (sEEG)-, is limited: the biomarkers are not strongly linked to the neurophysiological mechanisms affected in ALS.
The human motor system encompasses 2 sub-systems: the α motor system directly innervates the motor neurons and spinal interneurons and the γ system that modulates the sensors of the muscles' feedback reflex loops to indirectly contribute to muscle activations. These 2 systems form a neuromuscular communication and control network, through which neural signals are communicated to and from muscles for coordinated movement. In ALS, there is a disruption of the function of both upper and lower motor neurons. In the lower motor neurons, the degeneration of the α-motor system starts prior to the γ-system, thus changing the relative contribution of the α and γ system which distorts the patterns of neuromuscular communication in movements. It is therefore of interest to distinguish and dissociate the electrophysiological signatures that reflect sensorimotor network communication patterns pertaining to each sub-system in function and dysfunction, which in turn can act as biomarkers. In specific subgroups of ALS, i.e. Primary Lateral Sclerosis (PLS) and Progressive Muscle Atrophy (PMA) - there is selective degeneration of the upper or lower motor neurons respectively. Therefore, more specific changes in network communication patterns are to be expected.
To analyse the cybernetic characteristics (communication, control, and information transfer), electrophysiological signals need to be analysed from several points of the neuromuscular system as an interconnected network. This can be achieved by joint recording and advanced analysis of co-variability of patterns in the EMG/EEG, e.g. (directional) cortico-muscular coherence and directional network influences, during functional motor tasks. It is hypothesised that neuromuscular communication measures based on both EEG and EMG (indicators of pathophysiological change, measured as a network) better reflect ALS onset and subtypes than measures based on either EEG or EMG in isolation (indicators of structural change, measured at nodes).
Successful discrimination of the electrophysiological signatures can be used to diagnose ALS which may be also useful in terms of better patient care and the development of novel neuro-motor rehabilitation.
- Being tested
- 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)
- Keywords
- EEG, Corticomuscular coherence, Biomarkers, Electrophysiology, Neuromuscular disease, EMG
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Postpoliomyelitis Syndrome, Muscular Atrophy, Spinal, Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)Procedure or surgery
128 electrode EEG and 8 bipolar EMG or HD-EMG will be noninvasively recorded from electrodes placed in a montage over the scalp and arm muscles while the participant is resting or performing tasks designed to engage specific cortical networks of interest (cognitive, behavioural, motor 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: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG) | |
| Amyotrophic lateral sclerosis patients | Individuals from the Irish population (Irish Motorneuron Disease Register) with possible/probable/definitive diagnosis of ALS. Receives: Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG) | |
| Postpoliomyelitis syndrome | Individuals from the Irish population (Irish Motorneuron Disease Register) with postpoliomyelitis syndrome diagnosis. Receives: Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG) | |
| Spinal Muscular Atrophy | Individuals from the Irish population (Irish Motorneuron Disease Register) with spinal muscular atrophy diagnosis. Receives: Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
EEG-EMG signatures for reliable and early distinction between healthy people and ALS patient subgroups (specifically ALS, PLS, PMA, and SMA).
Cortico-muscular coherence (CMC) during functional motor tasks.
Measured: Baseline to final visit assessed up to 2 years after baseline
EEG-EEG signatures for reliable and early distinction between healthy people and ALS patient subgroups (specially ALS, PLS, PMA, and SMA)
Cortico-cortical coherence during functional motor tasks.
Measured: Baseline to final visit assesed up to 2 years after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2022
- Study start1 Oct 2015
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALS (Amyotrophic Lateral Sclerosis)Studies 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
- 400 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, Research Motor Neuron, 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
- NCT05663008
- Sponsor's protocol ID
- CRFSJ0136
- Acronym
- MotorMarker
- Status last verified
- Dec 2022
- First submitted
- 2 Dec 2022
- Last updated
- 23 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impairments of Neuro-muscular Communication in Motor-Neuron Disease: A Bio-Marker for Early and Personalised Diagnosis
- ClinicalTrials.gov ID
- NCT05663008
- Acronym / sponsor ID
- MotorMarker / CRFSJ0136
- Keywords
- EEG, Corticomuscular coherence, Biomarkers, Electrophysiology, Neuromuscular disease, EMG
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of Dublin, Trinity CollegeUniversity, hospital or other
- Collaborators
- Motor Neurone Disease Association, UK, Irish Research Council, Research Motor Neuron, IE, Thierry Latran Foundation, FR, ALS Association, USA
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 23 Dec 2022 (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.
Motor neuron disease (MND) or ALS is a nervous system disease. ALS leads to a loss of movement ability that eventually leads to death. At the moment, there is no known treatment for ALS. Early diagnosis in individuals improves clinical care and facilitates timely entry into clinical trials. However, current methods for diagnosis are primarily clinical, and to date, no cost-effective biomarkers have been developed. Our objective is to identify a robust non-invasive neurophysiological-based system that can be used both as a biomarker of disease onset, and a measurement of progression using quantitative EEG and surface EMG (bipolar and high-density).
The investigators postulate that analysing the joint recordings of EEG and EMG (bipolar or high-density) can give measures that better distinguish healthy people and ALS patient subgroups and that the findings can be developed as biomarkers of early diagnosis and disease progression.
Detailed description
Amyotrophic Laterals Sclerosis (ALS) or Motor Neuron Disease (MND) is a terminal neurodegenerative disease, that leads to progressive loss of motor function. Treatment of ALS remains an unresolved challenge and despite intensive research, diagnosis and therapy are not yet adequately personalised . New therapeutics and the quality of care after diagnosis can be enhanced by early diagnosis at the individual patient level, enabling tailored care and individualised treatment.
To personalise the diagnosis, there is a need for reliable quantitative biomarkers, for early detection of disease onset and to distinguish the different sub-types of the disease. Specifically, several biomarkers have been investigated for use in ALS, including Motor Unit Number Estimation (MUNE), Motor Unit Number Index (MUNIX), Cortical Excitability in Transcranial Magnetic Stimulation (TMS), EMG Inter-muscular Coherence, Magnetic Resonance (MR) and other imaging techniques, and EEG signatures. However, the diagnostic utility of these techniques, especially the inexpensive non-invasive recordings of electrical muscle activity - bipolar or high-density surface electromyography (sEMG), and electrical brain activity -surface electroencephalography (sEEG)-, is limited: the biomarkers are not strongly linked to the neurophysiological mechanisms affected in ALS.
The human motor system encompasses 2 sub-systems: the α motor system directly innervates the motor neurons and spinal interneurons and the γ system that modulates the sensors of the muscles' feedback reflex loops to indirectly contribute to muscle activations. These 2 systems form a neuromuscular communication and control network, through which neural signals are communicated to and from muscles for coordinated movement. In ALS, there is a disruption of the function of both upper and lower motor neurons. In the lower motor neurons, the degeneration of the α-motor system starts prior to the γ-system, thus changing the relative contribution of the α and γ system which distorts the patterns of neuromuscular communication in movements. It is therefore of interest to distinguish and dissociate the electrophysiological signatures that reflect sensorimotor network communication patterns pertaining to each sub-system in function and dysfunction, which in turn can act as biomarkers. In specific subgroups of ALS, i.e. Primary Lateral Sclerosis (PLS) and Progressive Muscle Atrophy (PMA) - there is selective degeneration of the upper or lower motor neurons respectively. Therefore, more specific changes in network communication patterns are to be expected.
To analyse the cybernetic characteristics (communication, control, and information transfer), electrophysiological signals need to be analysed from several points of the neuromuscular system as an interconnected network. This can be achieved by joint recording and advanced analysis of co-variability of patterns in the EMG/EEG, e.g. (directional) cortico-muscular coherence and directional network influences, during functional motor tasks. It is hypothesised that neuromuscular communication measures based on both EEG and EMG (indicators of pathophysiological change, measured as a network) better reflect ALS onset and subtypes than measures based on either EEG or EMG in isolation (indicators of structural change, measured at nodes).
Successful discrimination of the electrophysiological signatures can be used to diagnose ALS which may be also useful in terms of better patient care and the development of novel neuro-motor rehabilitation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Controls | – | Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis. |
| Amyotrophic lateral sclerosis patients | – | Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)Individuals from the Irish population (Irish Motorneuron Disease Register) with possible/probable/definitive diagnosis of ALS. |
| Postpoliomyelitis syndrome | – | Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)Individuals from the Irish population (Irish Motorneuron Disease Register) with postpoliomyelitis syndrome diagnosis. |
| Spinal Muscular Atrophy | – | Procedure: 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)Individuals from the Irish population (Irish Motorneuron Disease Register) with spinal muscular atrophy diagnosis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- MND (ALS, PLS, PMA, SMA, Polio or MS) patients will be recruited from the national MND/ALS register, an ongoing registry run in conjunction with Beaumont Hospital ALS clinic, run by Professor Orla Hardiman. Healthy controls will be recruited from the student population and age-matched controls from the general public, as well as a dataset of pre-consented healthy volunteers which is maintained at the Academic Unit of Neurology, Trinity College Dublin.
Key inclusion criteria (6 listed)
- age and gender-matched to patient groups
- the 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 (8 listed)
- History of neuromuscular
- neurological or active psychiatric disease disease
- history of reaction or allergy to recording environments, equipment and the recording gels.
- the presence of active psychiatric disease
- any medical condition associated with severe neuropathy (e.g. poorly controlled diabetes).
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 |
|---|---|---|
| 128 electrode electroencephalography (EEG), Bipolar surface electromyography (sEMG), High-density electromyography (HD-EMG)128 electrode EEG and 8 bipolar EMG or HD-EMG will be noninvasively recorded from electrodes placed in a montage over the scalp and arm muscles while the participant is resting or performing tasks designed to engage specific cortical networks of interest (cognitive, behavioural, motor and sensory) | Procedure or surgery | Amyotrophic lateral sclerosis patients, Controls, Postpoliomyelitis syndrome, Spinal Muscular Atrophy |
Primary outcome
EEG-EMG signatures for reliable and early distinction between healthy people and ALS patient subgroups (specifically ALS, PLS, PMA, and SMA).
Time frame: Baseline to final visit assessed up to 2 years after baseline
Cortico-muscular coherence (CMC) during functional motor tasks.
EEG-EEG signatures for reliable and early distinction between healthy people and ALS patient subgroups (specially ALS, PLS, PMA, and SMA)
Time frame: Baseline to final visit assesed up to 2 years after baseline
Cortico-cortical coherence during functional motor tasks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2022.
- Individual participant dataSharing planned: No
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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.
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 ALS (Amyotrophic Lateral Sclerosis) and Postpoliomyelitis Syndrome, 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 6 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 23 Dec 2022. 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?
This study is still under way. Results are not available in the source record yet.
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?
EEG-EMG signatures for reliable and early distinction between healthy people and ALS patient subgroups (specifically ALS, PLS, PMA, and SMA). (time frame: Baseline to final visit assessed up to 2 years after baseline). The study lists 2 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 23 Dec 2022.