Multiple SclerosisNCT07128160
Cortical Inhibition in Patients With Multiple Sclerosis
An observational study of Multiple Sclerosis, run by Assiut University.
Trial summary
1. To investigate the relationship between corticospinal inhibition and clinical, psychological, and cognitive features in MS patients. 2. To examine the association between corticospinal inhibition and radiological findings, including MRI lesions and white matter damage Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Clinical and Demographic Assessment, Corticospinal Inhibition Assessment and Radiological Assessment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2025to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: the sample size calculation was performed using EpI-Info 2002 software statistical package designed by World Health Organization (WHO) and by Centers for Disease Control and Prevention (CDC). The sample size was calculated based on the following considerations: 95% confidence level and according to a previous study (Chaves, A. R.,2024). Therefore, resulting sample size of 82 thus sample size increased to 90 Chaves, A. R., Tremblay, S., Pilutti, L., \& Ploughman, M. (2024). Lowered ratio of corticospinal excitation to inhibition predicts greater disability, poorer motor and cognitive function in multiple sclerosis. Heliyon, 10(15).
Who may be able to join
- Age 18 years or older.
- Diagnosis of RRMS based on the 2017 McDonald Criteria.
- Expanded Disability Status Scale (EDSS) score ≤ 6.5.
- On a stable dose of disease-modifying therapy (DMT) for at least 3 months or naeive patients not use DMT before
- Free of relapses or steroids treatment (at least 3 months after a relapse or corticosteroid therapy)
- Ability to give informed consent and complete neuropsychological assessments.
Who cannot join
- Presence of other neurological or psychiatric disorders (e.g., major depression, bipolar disorder, schizophrenia).
- History of alcohol or substance abuse.
- Contraindications to MRI (e.g., pacemakers, metallic implants) and TMS (i.e., history of seizures, presence of ferromagnetic implants in the head area).
- Medications known to alter the corticospinal excitability.
- Severe visual deficit, motor weakness, or intellectual impairment (as per the Mini-Mental State Exam score < 24).
About this study
Official title: The Relationship Between Neuropsychiatric, Radiological Findings and Cortical Inhibition in Patients With Multiple Sclerosis: A Hospital-based Study
- To investigate the relationship between corticospinal inhibition and clinical, psychological, and cognitive features in MS patients.
- To examine the association between corticospinal inhibition and radiological findings, including MRI lesions and white matter damage
Read the detailed description
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS), characterized by demyelinating white matter lesions and diffuse neurodegeneration. These pathological changes lead to variable and unpredictable clinical presentations and disease progression. Beyond motor and sensory deficits, MS is frequently associated with cognitive and emotional disturbances. Cognitive impairment affects 40-70% of patients, particularly in domains such as attention, processing speed, executive functions, and working memory-significantly impacting daily life and quality of care.
Alexithymia, a condition involving difficulty in identifying and describing emotions, externally oriented thinking, and limited imaginative ability, has been reported in a substantial proportion of patients, especially in progressive forms of the disease. It is frequently associated with sleep disturbances, anxiety, and depression.
Fatigue is one of the most burdensome and common symptoms in MS. It may present at any stage and is defined as a persistent lack of physical or mental energy that interferes with daily function. Fatigue may be classified as primary-linked directly to MS pathophysiology-or secondary, due to comorbid conditions, medication effects, or inactivity. Unlike general fatigue, MS-related fatigue is not relieved by rest and has a distinctly disabling nature.
Depression is another prevalent comorbidity, with lifetime prevalence in MS ranging widely. Its development reflects both the psychological burden of chronic disease and neurobiological mechanisms, such as inflammation and demyelination affecting mood circuits.
Given this wide spectrum of motor, cognitive, and emotional manifestations, comprehensive and multidimensional tools are essential for assessing the functional impact of MS. The Multiple Sclerosis Functional Composite (MSFC) is one such standardized, performance-based assessment. It captures core aspects of MS-related disability across three domains: ambulation (Timed 25-Foot Walk, T25FW), upper limb coordination (9-Hole Peg Test, 9HPT), and cognition (Paced Auditory Serial Addition Test, PASAT-3).
Magnetic resonance imaging (MRI) plays a pivotal role in both diagnosis and disease monitoring. Beyond identifying dissemination in time and space, advanced MRI techniques have linked symptom burden-particularly fatigue and cognitive deficits-to microstructural damage in normal-appearing white matter. This suggests that functional disconnection, rather than lesion volume alone, contributes to clinical manifestations.
Transcranial magnetic stimulation (TMS) provides a non-invasive, neurophysiological method to assess corticospinal excitability. When applied to the primary motor cortex, TMS elicits motor-evoked potentials (MEPs) that reflect both direct and trans-synaptic activation of motor pathways, offering insights into cortical inhibition and conduction properties in MS.
Despite advances in neuroimaging and functional assessments, the relationship between corticospinal inhibition and the heterogeneous symptomatology of multiple sclerosis-including fatigue, cognitive dysfunction, and emotional dysregulation-remains underexplored. Few studies have integrated transcranial magnetic stimulation (TMS) with clinical, cognitive, and radiological metrics in a multidimensional framework. This gap limits understanding of the neurophysiological substrates underlying these complex and disabling symptoms.
The present study aims to investigate the relationship between corticospinal inhibition, as assessed by TMS, and the clinical, psychological, cognitive, and radiological profiles of patients with multiple sclerosis. The hypothesis is that altered corticospinal inhibition will correlate with increased fatigue, cognitive dysfunction, alexithymia, and specific MRI abnormalities, reflecting the integrated neurophysiological basis of multiple sclerosis-related symptoms.
- Conditions
- Multiple Sclerosis
- Being tested
- Clinical and Demographic Assessment, Corticospinal Inhibition Assessment, Radiological Assessment
- Keywords
- multiple sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical and Demographic AssessmentOther
- Expanded Disability Status Scale (EDSS) (Kurtzke, 1983): This scale will be used for neurological disability assessment
- Multiple Sclerosis Functional Composite (MSFC): This composite will be used for the assessment of functional performance in patients with MS. It includes: a) Timed 25-foot walk (T25FW), b) Nine-hole peg test (9HPT) for both hands, and c) Paced auditory serial addition test (PASAT).
- Toronto Alexithymia Scale (TAS-20): This scale reports Alexithymia. It is a 20-item self-report questionnaire measuring three domains: Difficulty identifying feelings (DIF), Difficulty describing feelings (DDF), and externally oriented thinking (EOT). A score ≥ 61 indicates alexithymia (Bagby, Parker \& Taylor, 1994).
- Montreal Cognitive Assessment (MoCA), (Nasreddine ZS et al, 2005): a 30-point tool that investigates visuospatial abilities, language, attention, memory, abstraction, and orientation, with scores <26 suggestive of mild cognitive impairment
Corticospinal Inhibition AssessmentOther
Corticospinal inhibition will be evaluated using Transcranial Magnetic Stimulation (TMS) (Ayache et al., 2022; Chalah et al., 2018). All TMS assessments will be conducted according to international safety guidelines. The following parameters will be measured:
- Motor Evoked Potentials (MEPs) will be recorded from the abductor pollicis brevis muscle.
- Cortical silent period (CSP) will be assessed to measure corticospinal excitability and inhibition.
- The interhemispheric inhibition (IHI) is a parameter reflecting the transcallosal GABA-mediated inhibitory activity. It will be obtained at complete muscle rest using figure-of-eight coils (MC-B70; MagVenture), connected with a MagPro_R20 (Medtronic Inc., USA) generator connected to a butterfly coil.
Radiological AssessmentOther
All patients will undergo brain and spinal cord Magnetic Resonance Imaging (MRI) using a 1.5T scanner. Brain MRI sequences include: T1-weighted, T2-weighted, FLAIR, and post-contrast sequences. Spinal MRI (cervical and thoracic) includes T2-weighted and STIR sequences. Radiological assessment focused on:
- Number and location of T2/FLAIR lesions
- Presence of contrast-enhancing lesions
- Degree of brain atrophy (qualitatively)
- Spinal cord lesion load A neuroradiologist will review MRI findings, blinded to the clinical and neuropsychological data
| Study group | Role | What they receive |
|---|---|---|
| multiple sclerosis | patients with multiple sclerosis Receives: Other: Clinical and Demographic Assessment; Other: Corticospinal Inhibition Assessment; Other: Radiological Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor Evoked Potential (MEP)
Obtained using single-pulse transcranial magnetic stimulation over the primary motor cortex. Latency is defined as the time interval from the TMS pulse to the onset of the muscle response. Longer latencies may indicate impaired corticospinal conduction.
Measured: baseline
Cortical Silent Period (CSP)
Recorded during sustained voluntary muscle contraction using TMS. The silent period is the time during which voluntary electromyographic activity is suppressed following the motor evoked potential. CSP reflects intracortical inhibitory mechanisms.
Measured: baseline
Interhemispheric Inhibition (IHI)
The interhemispheric inhibition (IHI) is a parameter reflecting the transcallosal GABA-mediated inhibitory activity. It will be obtained at complete muscle rest using figure-of-eight coils (MC-B70; MagVenture)
Measured: baseline
Secondary outcomes (2)
Toronto Alexithymia Scale (TAS-20)
A 20-item self-report measure that evaluates difficulty in identifying feelings, difficulty in describing feelings, and externally oriented thinking. Each item is rated on a 5-point Likert scale, with higher scores indicating greater alexithymia.
Measured: baseline
Fatigue Severity Scale (FSS)
A self-reported questionnaire consisting of nine items that assess the impact of fatigue on daily functioning. Each item is scored on a 7-point Likert scale, with higher scores indicating greater fatigue severity.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2025
- Study start1 Nov 2025 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, abanoub bassem fikry ramzy, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07128160
- Sponsor's protocol ID
- cortical intibition in ms
- Status last verified
- Aug 2025
- First submitted
- 11 Aug 2025
- Last updated
- 17 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Neuropsychiatric, Radiological Findings and Cortical Inhibition in Patients With Multiple Sclerosis: A Hospital-based Study
- ClinicalTrials.gov ID
- NCT07128160
- Acronym / sponsor ID
- cortical intibition in ms
- Conditions
- Multiple Sclerosis
- Keywords
- multiple sclerosis
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Nov 2025 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 17 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To investigate the relationship between corticospinal inhibition and clinical, psychological, and cognitive features in MS patients.
- To examine the association between corticospinal inhibition and radiological findings, including MRI lesions and white matter damage
Detailed description
Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS), characterized by demyelinating white matter lesions and diffuse neurodegeneration. These pathological changes lead to variable and unpredictable clinical presentations and disease progression. Beyond motor and sensory deficits, MS is frequently associated with cognitive and emotional disturbances. Cognitive impairment affects 40-70% of patients, particularly in domains such as attention, processing speed, executive functions, and working memory-significantly impacting daily life and quality of care.
Alexithymia, a condition involving difficulty in identifying and describing emotions, externally oriented thinking, and limited imaginative ability, has been reported in a substantial proportion of patients, especially in progressive forms of the disease. It is frequently associated with sleep disturbances, anxiety, and depression.
Fatigue is one of the most burdensome and common symptoms in MS. It may present at any stage and is defined as a persistent lack of physical or mental energy that interferes with daily function. Fatigue may be classified as primary-linked directly to MS pathophysiology-or secondary, due to comorbid conditions, medication effects, or inactivity. Unlike general fatigue, MS-related fatigue is not relieved by rest and has a distinctly disabling nature.
Depression is another prevalent comorbidity, with lifetime prevalence in MS ranging widely. Its development reflects both the psychological burden of chronic disease and neurobiological mechanisms, such as inflammation and demyelination affecting mood circuits.
Given this wide spectrum of motor, cognitive, and emotional manifestations, comprehensive and multidimensional tools are essential for assessing the functional impact of MS. The Multiple Sclerosis Functional Composite (MSFC) is one such standardized, performance-based assessment. It captures core aspects of MS-related disability across three domains: ambulation (Timed 25-Foot Walk, T25FW), upper limb coordination (9-Hole Peg Test, 9HPT), and cognition (Paced Auditory Serial Addition Test, PASAT-3).
Magnetic resonance imaging (MRI) plays a pivotal role in both diagnosis and disease monitoring. Beyond identifying dissemination in time and space, advanced MRI techniques have linked symptom burden-particularly fatigue and cognitive deficits-to microstructural damage in normal-appearing white matter. This suggests that functional disconnection, rather than lesion volume alone, contributes to clinical manifestations.
Transcranial magnetic stimulation (TMS) provides a non-invasive, neurophysiological method to assess corticospinal excitability. When applied to the primary motor cortex, TMS elicits motor-evoked potentials (MEPs) that reflect both direct and trans-synaptic activation of motor pathways, offering insights into cortical inhibition and conduction properties in MS.
Despite advances in neuroimaging and functional assessments, the relationship between corticospinal inhibition and the heterogeneous symptomatology of multiple sclerosis-including fatigue, cognitive dysfunction, and emotional dysregulation-remains underexplored. Few studies have integrated transcranial magnetic stimulation (TMS) with clinical, cognitive, and radiological metrics in a multidimensional framework. This gap limits understanding of the neurophysiological substrates underlying these complex and disabling symptoms.
The present study aims to investigate the relationship between corticospinal inhibition, as assessed by TMS, and the clinical, psychological, cognitive, and radiological profiles of patients with multiple sclerosis. The hypothesis is that altered corticospinal inhibition will correlate with increased fatigue, cognitive dysfunction, alexithymia, and specific MRI abnormalities, reflecting the integrated neurophysiological basis of multiple sclerosis-related symptoms.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| multiple sclerosis | – | Other: Clinical and Demographic Assessment, Other: Corticospinal Inhibition Assessment, Other: Radiological Assessmentpatients with multiple sclerosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- the sample size calculation was performed using EpI-Info 2002 software statistical package designed by World Health Organization (WHO) and by Centers for Disease Control and Prevention (CDC). The sample size was calculated based on the following considerations: 95% confidence level and according to a previous study (Chaves, A. R.,2024). Therefore, resulting sample size of 82 thus sample size increased to 90 Chaves, A. R., Tremblay, S., Pilutti, L., \& Ploughman, M. (2024). Lowered ratio of corticospinal excitation to inhibition predicts greater disability, poorer motor and cognitive function in multiple sclerosis. Heliyon, 10(15).
Key inclusion criteria (6 listed)
- Age 18 years or older.
- Diagnosis of RRMS based on the 2017 McDonald Criteria.
- Expanded Disability Status Scale (EDSS) score ≤ 6.5.
- On a stable dose of disease-modifying therapy (DMT) for at least 3 months or naeive patients not use DMT before
- Free of relapses or steroids treatment (at least 3 months after a relapse or corticosteroid therapy)
Key exclusion criteria (5 listed)
- Presence of other neurological or psychiatric disorders (e.g., major depression, bipolar disorder, schizophrenia).
- History of alcohol or substance abuse.
- Contraindications to MRI (e.g., pacemakers, metallic implants) and TMS (i.e., history of seizures, presence of ferromagnetic implants in the head area).
- Medications known to alter the corticospinal excitability.
- Severe visual deficit, motor weakness, or intellectual impairment (as per the Mini-Mental State Exam score < 24).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical and Demographic Assessment1. Expanded Disability Status Scale (EDSS) (Kurtzke, 1983): This scale will be used for neurological disability assessment 2. Multiple Sclerosis Functional Composite (MSFC): This composite will be used for the assessment of functional performance in patients with MS. It includes: a) Timed 25-foot walk (T25FW), b) Nine-hole peg test (9HPT) for both hands, and c) Paced auditory serial addition test (PASAT). 3. Toronto Alexithymia Scale (TAS-20): This scale reports Alexithymia. It is a 20-item self-report questionnaire measuring three domains: Difficulty identifying feelings (DIF), Difficulty describing feelings (DDF), and externally oriented thinking (EOT). A score ≥ 61 indicates alexithymia (Bagby, Parker \& Taylor, 1994). 4. Montreal Cognitive Assessment (MoCA), (Nasreddine ZS et al, 2005): a 30-point tool that investigates visuospatial abilities, language, attention, memory, abstraction, and orientation, with scores <26 suggestive of mild cognitive impairment | Other | multiple sclerosis |
| Corticospinal Inhibition AssessmentCorticospinal inhibition will be evaluated using Transcranial Magnetic Stimulation (TMS) (Ayache et al., 2022; Chalah et al., 2018). All TMS assessments will be conducted according to international safety guidelines. The following parameters will be measured: 1. Motor Evoked Potentials (MEPs) will be recorded from the abductor pollicis brevis muscle. 2. Cortical silent period (CSP) will be assessed to measure corticospinal excitability and inhibition. 3. The interhemispheric inhibition (IHI) is a parameter reflecting the transcallosal GABA-mediated inhibitory activity. It will be obtained at complete muscle rest using figure-of-eight coils (MC-B70; MagVenture), connected with a MagPro_R20 (Medtronic Inc., USA) generator connected to a butterfly coil. | Other | multiple sclerosis |
| Radiological AssessmentAll patients will undergo brain and spinal cord Magnetic Resonance Imaging (MRI) using a 1.5T scanner. Brain MRI sequences include: T1-weighted, T2-weighted, FLAIR, and post-contrast sequences. Spinal MRI (cervical and thoracic) includes T2-weighted and STIR sequences. Radiological assessment focused on: * Number and location of T2/FLAIR lesions * Presence of contrast-enhancing lesions * Degree of brain atrophy (qualitatively) * Spinal cord lesion load A neuroradiologist will review MRI findings, blinded to the clinical and neuropsychological data | Other | multiple sclerosis |
Primary outcome
Motor Evoked Potential (MEP)
Time frame: baseline
Obtained using single-pulse transcranial magnetic stimulation over the primary motor cortex. Latency is defined as the time interval from the TMS pulse to the onset of the muscle response. Longer latencies may indicate impaired corticospinal conduction.
Cortical Silent Period (CSP)
Time frame: baseline
Recorded during sustained voluntary muscle contraction using TMS. The silent period is the time during which voluntary electromyographic activity is suppressed following the motor evoked potential. CSP reflects intracortical inhibitory mechanisms.
Interhemispheric Inhibition (IHI)
Time frame: baseline
The interhemispheric inhibition (IHI) is a parameter reflecting the transcallosal GABA-mediated inhibitory activity. It will be obtained at complete muscle rest using figure-of-eight coils (MC-B70; MagVenture)
2 secondary outcomes
Toronto Alexithymia Scale (TAS-20)
Time frame: baseline
Fatigue Severity Scale (FSS)
Time frame: baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motor Evoked Potential (MEP) (time frame: baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.