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EEG and TMS-based Biomarkers of ALS, MS and FTD

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ClinicalTrials.gov Identifier: NCT04918251
Recruitment Status : Recruiting
First Posted : June 8, 2021
Last Update Posted : June 8, 2021
Sponsor:
Collaborators:
Motor Neurone Disease Association, UK
Irish Research Council, IE
Health Research Board, IE
Research Motor Neurone, IE
Thierry Latran Foundation, FR
ALS Association, USA
Information provided by (Responsible Party):
Orla Hardiman, University of Dublin, Trinity College

Brief Summary:
The purpose of this observational study is to improve understanding of the biology of why ALS, MS and FTD have different effects on different people and facilitate better measurement of the disease in future drug testing. To do this, brain and spinal cord neural network functionality will be measured over time, in addition to profiling of movement and non-movement symptoms, in large groups of patients, as well as in a population-based sample of the healthy population. Patterns of dysfunction which relate to patients' diagnosis and coinciding and future symptoms which align with categories of patients with similar prognoses will be investigated and their ability to predict incident patients' symptoms in future will be measured.

Condition or disease Intervention/treatment
Amyotrophic Lateral Sclerosis Frontotemporal Dementia Multiple Sclerosis Procedure: 128 electrode electroencephalography (EEG) Procedure: Transcranial magnetic stimulation (TMS)

Detailed Description:
The aim of this project is to characterize spatiotemporal patterns of central nervous system dysfunction that correlate with clinical features of ALS, MS and FTD, to provide non-invasive electrophysiological measurements that can be used in a clinical setting to inform stratification of patients in clinical trials, and to provide data driven diagnostic and prognostic biomarkers and objective clinical trial outcome measures. Such dysfunction will be investigated by recording single- and paired-pulse transcranial magnetic stimulation (TMS)-associated electromyography (EMG) during rest and by recording electroencephalography (EEG) during rest and during cognitive-motor tasks.

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Investigation of EEG and TMS-based Biomarkers of Amyotrophic Lateral Sclerosis, Multiple Sclerosis and Frontotemporal Dementia
Actual Study Start Date : September 2012
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : April 2023


Group/Cohort Intervention/treatment
Controls
Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis
Procedure: 128 electrode electroencephalography (EEG)
128 electrode EEG will be non-invasively recorded from electrodes placed in a montage over the scalp while the participant is resting or performing tasks designed to engage specific cortical motor networks of interest (cognitive, behavioural, motor and sensory)

Procedure: Transcranial magnetic stimulation (TMS)
Single and paired pulse TMS protocol will be delivered while surface bipolar EMG is recorded over hand muscles to interrogate corticospinal tract function and cortical motor network component functions

Amyotrophic lateral sclerosis patients Procedure: 128 electrode electroencephalography (EEG)
128 electrode EEG will be non-invasively recorded from electrodes placed in a montage over the scalp while the participant is resting or performing tasks designed to engage specific cortical motor networks of interest (cognitive, behavioural, motor and sensory)

Procedure: Transcranial magnetic stimulation (TMS)
Single and paired pulse TMS protocol will be delivered while surface bipolar EMG is recorded over hand muscles to interrogate corticospinal tract function and cortical motor network component functions

Multiple sclerosis patients Procedure: 128 electrode electroencephalography (EEG)
128 electrode EEG will be non-invasively recorded from electrodes placed in a montage over the scalp while the participant is resting or performing tasks designed to engage specific cortical motor networks of interest (cognitive, behavioural, motor and sensory)

Procedure: Transcranial magnetic stimulation (TMS)
Single and paired pulse TMS protocol will be delivered while surface bipolar EMG is recorded over hand muscles to interrogate corticospinal tract function and cortical motor network component functions

Frontotemporal dementia patients Procedure: 128 electrode electroencephalography (EEG)
128 electrode EEG will be non-invasively recorded from electrodes placed in a montage over the scalp while the participant is resting or performing tasks designed to engage specific cortical motor networks of interest (cognitive, behavioural, motor and sensory)

Procedure: Transcranial magnetic stimulation (TMS)
Single and paired pulse TMS protocol will be delivered while surface bipolar EMG is recorded over hand muscles to interrogate corticospinal tract function and cortical motor network component functions




Primary Outcome Measures :
  1. Diagnosis-related difference in EEG or TMS measurements [ Time Frame: Baseline recording ]
    Differences in single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between those within each patient cohort and controls

  2. Prognosis-related EEG or TMS measurements [ Time Frame: Baseline recording ]
    Patient cohort single or paired pulse TMS measures or time and/or frequency domain EEG characteristics which show significant correlation to cognitive, behavioural, motor and/or sensory task performance, to disease duration or to survival time

  3. Diagnosis-related changes in EEG or TMS measurements [ Time Frame: Baseline to final visit assessed up to 2 years after baseline ]
    Differences in rate of change (slope) across time of single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between those within each patient cohort relative to controls

  4. Prognosis-related changes in EEG or TMS measurements [ Time Frame: Baseline to final visit assessed up to 2 years after baseline ]
    Rates of change (slope) across time of patient cohort single or paired pulse TMS measures or time and/or frequency domain EEG characteristics which show significant correlation to cognitive, behavioural, motor and/or sensory task performance, to disease duration or to survival time


Secondary Outcome Measures :
  1. Diagnosis-specific changes in EEG or TMS measurements [ Time Frame: Baseline to final visit assessed up to 2 years after baseline ]
    Differences in rate of change (slope) across time of single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between patient cohorts

  2. Diagnosis-specific difference in EEG or TMS measurements [ Time Frame: Baseline recording ]
    Differences in single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between patient cohorts



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy controls and patients diagnosed with ALS, FTD or MS
Criteria

Inclusion criteria:

  • Age >18 years and able to give informed written or verbal (in the presence of two witnesses) consent.
  • In the case of non-control subjects, a clinical diagnosis of:

    (i) Probable frontotemporal dementia (FTD) including behavioural variant FTD, semantic dementia or primary progressive aphasia) with supportive brain imaging or known FTD causing genetic mutation (ii) Multiple sclerosis (MS) according to the McDonald criteria (Polman et al., 2011) or (iii) Possible, probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial Criteria Revised (Brooks et al. 2000)

Exclusion criteria:

  • Any diagnosed neurological/muscular disease other than ALS, MS or FTD
  • Use of neuro- or myo-modulatory medications except riluzole
  • Inability to participate due to disease-related motor symptoms (e.g. inability to sit for the required time or click the mouse to respond)
  • Upper body metallic implants
  • History of seizure disorders in the participant or immediate family members
  • Anxiety-induced fainting
  • Regular migraine
  • Evidence of significant respiratory insufficiency
  • Sleep time >2 hours below normal and/or alcohol consumption the night before data collection (in which case, recording session will be rescheduled).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04918251


Contacts
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Contact: Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN +353 1 896 4497 hardimao@tcd.ie
Contact: Roisin McMackin, BA PhD 01 896 4497 mcmackr@tcd.ie

Locations
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Ireland
Academic Unit of Neurology, Trinity College Dublin, The University of Dublin Recruiting
Dublin, Leinster, Ireland, Dublin 2
Contact: Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN    018964497    hardimao@tcd.ie   
Contact: Roisin McMackin, BA PhD    0894888697    mcmackr@tcd.ie   
Sponsors and Collaborators
University of Dublin, Trinity College
Motor Neurone Disease Association, UK
Irish Research Council, IE
Health Research Board, IE
Research Motor Neurone, IE
Thierry Latran Foundation, FR
ALS Association, USA
Investigators
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Principal Investigator: Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
Publications of Results:

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Responsible Party: Orla Hardiman, Professor of Neurology, University of Dublin, Trinity College
ClinicalTrials.gov Identifier: NCT04918251    
Other Study ID Numbers: CRFSJ00170
CRFSJ00171 ( Other Identifier: St James' Hospital Clinical Research Facility, Dublin )
First Posted: June 8, 2021    Key Record Dates
Last Update Posted: June 8, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Due to ethical constraint and the time required for data quality checks, data will only be made available in fully anonymised format following publication of results.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Orla Hardiman, University of Dublin, Trinity College:
EEG
TMS
Neurodegeneration
Network
Electrophysiology
Biomarkers
Cognitive
Behavioural
Motor
Additional relevant MeSH terms:
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Multiple Sclerosis
Dementia
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Brain Diseases
Central Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Neuromuscular Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Frontotemporal Lobar Degeneration
Aphasia
Speech Disorders
Language Disorders
Communication Disorders