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

Sponsor

University of Dublin, Trinity College (Other)

Overall Status

Recruiting

CT.gov ID

NCT04918251

Collaborator

Motor Neurone Disease Association, UK (Other), Irish Research Council, IE (Other), Health Research Board, IE (Other), Research Motor Neurone, IE (Other), Thierry Latran Foundation, FR (Other), ALS Association, USA (Other)

400

Enrollment

Location

126.9

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

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	Phase
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.

Study Design

Study Type:

Observational

Anticipated 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 :

Sep 1, 2012

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

Diagnosis-related difference in EEG or TMS measurements [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
Prognosis-related EEG or TMS measurements [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
Diagnosis-related changes in EEG or TMS measurements [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
Prognosis-related changes in EEG or TMS measurements [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).