Neurophysiological Assessment in Patients With Multiple Sclerosis

NCT04997343 | Unknown

• 1 other identifier: 6357
• Study Type: interventional
• Target: 128
• Locations: 0 countries
• Sites: N/A

Brief Summary

Main aim of this study will be the evaluation of the neurophysiological techniques of Transcranial Magnetic Stimulation (TMS) via electroencephalography (EEG) co-registration (TMS-EEG) with the study of TEPs (TEP: transcranial evoked potentials) as surrogates of white matter and grey matter functional integrity in patients with Multiple Sclerosis (MS). Data will be compared with those obtained from a group of healthy control subjects. Secondary aim will be the longitudinal evaluation of these neurophysiological parameters in MS patients during routine clinical and radiological evaluations, performed according to clinical practice, for 12 months. To this aim a longitudinal multicenter study will be carried out, interventional (for neurophysiological techniques) and observational (for clinical and radiological evaluations), which involves the enrollment of 64 patients diagnosed with MS. Patients will keep their usual therapeutic regimen and their usual clinical-radiological checks according to clinical practice. The control group will consist of 64 healthy subjects, enrolled with prior written informed consent, age and sex-matched with MS patients and selected among the caregivers of the patients. Healthy subjects will only undergo neurophysiological assessment at baseline. The neurophysiological evaluation will include the study of the propagation of potentials induced by stimulation. This method allows the study of cortical responses in terms of time domain and frequency, obtaining a measurement of interhemispheric connectivity and of microstructural and functional integrity of white matter. In the same way, these methods allow the assessment of grey matter integrity through the study of intracortical excitability.

Conditions

Multiple Sclerosis; Demyelinating Disease; Inflammatory Disease

Keywords

neurophysiology; TMS-EEG; multiple sclerosis

Outcome Measures

Primary Outcomes (11)

• Changes of Global cortico-cortical myelination

  Power of the dominant frequency peak of the global electroencephalography (EEG) signal.

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of the Cortical-cortical coherence

  Coherence between EEG signals recorded from distant channels.

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of the Local cortical-cortical myelination (motor)

  Power of the dominant frequency peak of the local EEG signal on primary motor cortex (M1).

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of the Trans-callosal axonal myelination

  Cortico-cortical coherence between EEG signals recorded on primary motor cortex (M1) areas bilaterally.

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of Interhemispheric signal propagation (iSP)

  TMS-EMG measurement of the ipsilateral silent period (IpSP)

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of TMS-EEG measurement of the functional integrity of the grey matter:

  Amplitude of the early components of Transcranial evoked potentials (TEPs).

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of TMS-EMG measurement of the functional integrity of the grey matter:

  Resting Motor Threshold- (RMT)

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of clinical outcome measures

  Clinical disability will be monitored with the Expanded Disability Status Scale (EDSS), performed by the same neurologist at each timepoint.

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of the Multiple Sclerosis Functional Composite (MSFC)

  To assess walking, lower limb functionality, upper limb dexterity and cognitive function.

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of radiological outcome measures

  Evaluation of the lesion load

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

• Changes of magnetic resonance imaging (MRI) number of lesions in T2

  Evaluation of new lesions in T2 compared to the previous evaluation.

  Baseline (T0) and at 6 and 12 months. Healthy controls will undergo only the neurophysiological evaluation at baseline.

Study Arms (2)

MS patients

EXPERIMENTAL

All MS patients will undergo clinical and neurophysiological evaluation at baseline (T0). The baseline will consider the radiological data of disease activity obtained from the most recently performed MRI according to clinical practice. These evaluations will be repeated according to clinical practice in patients taking DMT or every 6 months, in a stable condition or according to the indication of the treating neurologist in case of disease reactivation. A one-year neurophysiological, clinical and radiological observation is foreseen. Healthy subjects will undergo only the neurophysiological evaluation at baseline.

Other: Neurophysiological assessment; Other: clinical assessment

Healthy controls

OTHER

Healthy subjects will undergo only the neurophysiological evaluation at baseline.

Other: Neurophysiological assessment

Interventions

Neurophysiological assessment OTHER

EMG will be recorded from the Abductor pollicis brevis muscle (APB) with surface electrodes. EEG will be recorded with a 32-channel elastic cap via a TMS compatible system. TMS will be performed using a Magstim 200 stimulator with a 90 mm figure-of-eight coil localized on motor and non-motor areas using a neuronavigation system together with an optical tracking system. Coordinates for neuronavigation will be calculated in the MNI space and fit of each participant's anatomical MRI. Three minutes of continuous-EEG will be recorded with subjects at rest. Single-pulse neuronavigated TMS (sp-TMS) will be delivered at rest below the resting motor threshold intensity (RMT) over the APB hotspot on M1 during concurrent EEG recording. In a final block, the subject will maintain a voluntary muscle contraction (50% of the maximal voluntary contraction) of the left APB, and sp-TMS will be delivered at 130% RMT over the ipsilateral APB hotspot in order to record the lpSP.

Healthy controls; MS patients

clinical assessment OTHER

Clinical evaluation, performed at each time point, will include: * The assessment of clinical disability using EDSS score * The multiple sclerosis functional composite (MSFC), a three-part quantitative objective measure of neurologic function, measuring lower limbs (timed 25-foot walk \[T25FW\]), upper limbs (nine-hole peg test \[9HPT\]) and cognitive (three-second paced auditory serial addition test \[PASAT3\]) function. In order to reduce inter-rater variability, the same physician/technician with adequate training will administer all three tests. The patient should feel comfortable with the situation. Examiner should explain the instructions in a professional but friendly way and let the patient ask any questions before starting the tests. Examiner should write down the test results, as well as any situation that disturbs the performance of patient. Examiner should not provide direct feedback to the patient about his/her performance

MS patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MS diagnosis according to the latest McDonald criteria

You may not qualify if:

• other neurological or immunological diseases
• clinical relapses in the 30 days prior to the clinical and neurophysiological evaluation;
• presence of conditions that contraindicate the execution of Transcranial Magnetic Stimulation (TMS) methods (history of epilepsy, pacemaker, recent head injury).

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Related Publications (27)

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MeSH Terms

Conditions

Multiple Sclerosis; Demyelinating Diseases

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Diego Centonze, MD, PhD

  Unit of Neurology, IRCCS Neuromed, Pozzilli, IS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonella Conte, MD, PhD

CONTACT

00393466584811; antonella.conte@uniroma1.it

Rita Botti

CONTACT

000649914512; rita.botti@uniroma1.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: In this multicenter, longitudinal, interventional (for TMS-EEG) -observational (for clinical and radiological variables obtained according to clinical practice) case-control study, all participants will undergo clinical and neurophysiological evaluation at baseline (T0). The baseline will consider the radiological data of disease activity. These evaluations will be repeated according to clinical practice in patients taking Disease modifying therapies (DMTs) or every 6 months, in a stable condition or according to the indication of the treating neurologist in case of disease reactivation. A one-year neurophysiological, clinical and radiological observation is foreseen. Healthy subjects will undergo only the neurophysiological evaluation at baseline. For the study, no hospital diagnostic equipment will be used, but machinery present in the research laboratories, for research use only, bearing the CE mark.

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: August 9, 2021
• Study Start: October 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: September 1, 2023
• Last Updated: August 9, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: starting 3 months after data pubblication
• Access Criteria: research group focused in neurophysiological investigations in patients with multiple sclerosis