EEG and TMS-based Biomarkers of ALS, MS and FTD
Investigation of EEG and TMS-based Biomarkers of Amyotrophic Lateral Sclerosis, Multiple Sclerosis and Frontotemporal Dementia
2 other identifiers
observational
400
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Sep 2012
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2012
CompletedFirst Submitted
Initial submission to the registry
April 1, 2021
CompletedFirst Posted
Study publicly available on registry
June 8, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2023
CompletedJune 8, 2021
June 1, 2021
10.4 years
April 1, 2021
June 2, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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
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
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
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 Outcomes (2)
Diagnosis-specific changes in EEG or TMS measurements
Baseline to final visit assessed up to 2 years after baseline
Diagnosis-specific difference in EEG or TMS measurements
Baseline recording
Study Arms (4)
Controls
Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis
Amyotrophic lateral sclerosis patients
Multiple sclerosis patients
Frontotemporal dementia patients
Interventions
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)
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
Eligibility Criteria
Healthy controls and patients diagnosed with ALS, FTD or MS
You may qualify if:
- 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)
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Dublin, Trinity Collegelead
- Motor Neurone Disease Association, UKcollaborator
- Irish Research Council, IEcollaborator
- Health Research Board, IEcollaborator
- Research Motor Neurone, IEcollaborator
- Thierry Latran Foundation, FRcollaborator
- ALS Association, USAcollaborator
Study Sites (1)
Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
Dublin, Leinster, Dublin 2, Ireland
Related Publications (7)
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.
PMID: 30735860RESULTDukic 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.
PMID: 31348605RESULTMcMackin 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.
PMID: 32318719RESULTMcMackin 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.
PMID: 33395671RESULTIyer 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.
PMID: 28861032RESULTNasseroleslami 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.
PMID: 29136131RESULTIyer 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.
PMID: 26091258RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN
Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Neurology
Study Record Dates
First Submitted
April 1, 2021
First Posted
June 8, 2021
Study Start
September 1, 2012
Primary Completion
February 1, 2023
Study Completion
April 1, 2023
Last Updated
June 8, 2021
Record last verified: 2021-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, 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.
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.