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

NCT ID: NCT04918251

Last Updated: 2021-06-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

400 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-09-30

Study Completion Date

2023-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Amyotrophic Lateral Sclerosis Frontotemporal Dementia Multiple Sclerosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Controls

Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis

128 electrode electroencephalography (EEG)

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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

128 electrode electroencephalography (EEG)

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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

128 electrode electroencephalography (EEG)

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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

128 electrode electroencephalography (EEG)

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

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

Interventions

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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)

Intervention Type 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

Intervention Type PROCEDURE

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Motor Neurone Disease Association, UK

UNKNOWN

Sponsor Role collaborator

Irish Research Council, IE

UNKNOWN

Sponsor Role collaborator

Health Research Board, IE

UNKNOWN

Sponsor Role collaborator

Research Motor Neurone, IE

UNKNOWN

Sponsor Role collaborator

Thierry Latran Foundation, FR

UNKNOWN

Sponsor Role collaborator

ALS Association, USA

UNKNOWN

Sponsor Role collaborator

University of Dublin, Trinity College

OTHER

Sponsor Role lead

Responsible Party

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Orla Hardiman

Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN

Role: PRINCIPAL_INVESTIGATOR

Academic Unit of Neurology, Trinity College Dublin, The University of Dublin

Locations

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Academic Unit of Neurology, Trinity College Dublin, The University of Dublin

Dublin, Leinster, Ireland

Site Status RECRUITING

Countries

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Ireland

Central Contacts

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Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN

Role: CONTACT

+353 1 896 4497

Roisin McMackin, BA PhD

Role: CONTACT

01 896 4497

Facility Contacts

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Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN

Role: primary

018964497

Roisin McMackin, BA PhD

Role: backup

0894888697

References

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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 amyotrophic lateral sclerosis. Neuroimage Clin. 2019;22:101707. doi: 10.1016/j.nicl.2019.101707. Epub 2019 Feb 2.

Reference Type RESULT
PMID: 30735860 (View on PubMed)

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 network disruption in amyotrophic lateral sclerosis. Hum Brain Mapp. 2019 Nov 1;40(16):4827-4842. doi: 10.1002/hbm.24740. Epub 2019 Jul 26.

Reference Type RESULT
PMID: 31348605 (View on PubMed)

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 Executive Impairment in Amyotrophic Lateral Sclerosis. Cereb Cortex. 2020 Jul 30;30(9):4834-4846. doi: 10.1093/cercor/bhaa076.

Reference Type RESULT
PMID: 32318719 (View on PubMed)

McMackin R, Dukic S, Costello E, Pinto-Grau M, Keenan O, Fasano A, Buxo T, Heverin M, Reilly R, Pender N, Hardiman O, Nasseroleslami B. Sustained attention to response task-related beta oscillations relate to performance and provide a functional biomarker in ALS. J Neural Eng. 2021 Feb 25;18(2). doi: 10.1088/1741-2552/abd829.

Reference Type RESULT
PMID: 33395671 (View on PubMed)

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 Sclerosis. Front Neurol. 2017 Aug 15;8:395. doi: 10.3389/fneur.2017.00395. eCollection 2017.

Reference Type RESULT
PMID: 28861032 (View on PubMed)

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 Lateral Sclerosis. Cereb Cortex. 2019 Jan 1;29(1):27-41. doi: 10.1093/cercor/bhx301.

Reference Type RESULT
PMID: 29136131 (View on PubMed)

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: 10.1371/journal.pone.0128682. eCollection 2015.

Reference Type RESULT
PMID: 26091258 (View on PubMed)

Other Identifiers

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CRFSJ00171

Identifier Type: OTHER

Identifier Source: secondary_id

CRFSJ00170

Identifier Type: -

Identifier Source: org_study_id

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