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

Multiple Sclerosis Clinical Trial

Official title:

Investigation of EEG and TMS-based Biomarkers of Amyotrophic Lateral Sclerosis, Multiple Sclerosis and Frontotemporal Dementia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04918251
• Other study ID #: CRFSJ00170
• Secondary ID: CRFSJ00171
• Status: Recruiting
• Start date: September 2012
• Est. completion date: April 2023

Study information

• Verified date: June 2021
• Source: University of Dublin, Trinity College
• Contact: Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN
• Phone: +353 1 896 4497
• Email: hardimao[@]tcd.ie
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: April 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Aphasia, Primary Progressive
• Dementia
• Frontotemporal Dementia
• Motor Neuron Disease
• Multiple Sclerosis
• Pick Disease of the Brain
• Sclerosis

Intervention

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)
• 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

Locations

Country	Name	City	State
Ireland	Academic Unit of Neurology, Trinity College Dublin, The University of Dublin	Dublin	Leinster

Sponsors (7)

Lead Sponsor	Collaborator
University of Dublin, Trinity College	ALS Association, USA, Health Research Board, IE, Irish Research Council, IE, Motor Neurone Disease Association, UK, Research Motor Neurone, IE, Thierry Latran Foundation, FR

Country where clinical trial is conducted

Ireland, 

References & Publications (7)

Dukic S, McMackin R, Buxo T, Fasano A, Chipika R, Pinto-Grau M, Costello E, Schuster C, Hammond M, Heverin M, Coffey A, Broderick M, Iyer PM, Mohr K, Gavin B, Pender N, Bede P, Muthuraman M, Lalor EC, Hardiman O, Nasseroleslami B. Patterned functional net — View Citation

Iyer PM, Egan C, Pinto-Grau M, Burke T, Elamin M, Nasseroleslami B, Pender N, Lalor EC, Hardiman O. Functional Connectivity Changes in Resting-State EEG as Potential Biomarker for Amyotrophic Lateral Sclerosis. PLoS One. 2015 Jun 19;10(6):e0128682. doi: 1 — View Citation

Iyer PM, Mohr K, Broderick M, Gavin B, Burke T, Bede P, Pinto-Grau M, Pender NP, McLaughlin R, Vajda A, Heverin M, Lalor EC, Hardiman O, Nasseroleslami B. Mismatch Negativity as an Indicator of Cognitive Sub-Domain Dysfunction in Amyotrophic Lateral Scler — View Citation

McMackin R, Dukic S, Broderick M, Iyer PM, Pinto-Grau M, Mohr K, Chipika R, Coffey A, Buxo T, Schuster C, Gavin B, Heverin M, Bede P, Pender N, Lalor EC, Muthuraman M, Hardiman O, Nasseroleslami B. Dysfunction of attention switching networks in amyotrophi — View Citation

McMackin R, Dukic S, Costello E, Pinto-Grau M, Fasano A, Buxo T, Heverin M, Reilly R, Muthuraman M, Pender N, Hardiman O, Nasseroleslami B. Localization of Brain Networks Engaged by the Sustained Attention to Response Task Provides Quantitative Markers of — View Citation

McMackin R, Dukic S, Costello E, Pinto-Grau M, Keenan O, Fasano A, Buxo T, Heverin M, Reilly RB, Pender N, Hardiman O, Nasseroleslami B. Sustained attention to response task-related beta oscillations relate to performance and provide a functional biomarke — View Citation

Nasseroleslami B, Dukic S, Broderick M, Mohr K, Schuster C, Gavin B, McLaughlin R, Heverin M, Vajda A, Iyer PM, Pender N, Bede P, Lalor EC, Hardiman O. Characteristic Increases in EEG Connectivity Correlate With Changes of Structural MRI in Amyotrophic La — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnosis-related difference in EEG or TMS measurements	Differences in single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between those within each patient cohort and controls	Baseline recording
Primary	Prognosis-related EEG or TMS measurements	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	Baseline recording
Primary	Diagnosis-related changes in EEG or TMS measurements	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	Baseline to final visit assessed up to 2 years after baseline
Primary	Prognosis-related changes in EEG or TMS measurements	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	Baseline to final visit assessed up to 2 years after baseline
Secondary	Diagnosis-specific changes in EEG or TMS measurements	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	Baseline to final visit assessed up to 2 years after baseline
Secondary	Diagnosis-specific difference in EEG or TMS measurements	Differences in single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between patient cohorts	Baseline recording