Comparative Effectiveness of Ipsilesional High-frequency rTMS, Contralesional Continuous Burst Theta rTMS, and Sham rTMS, Each Combined With Physiotherapy, in Subacute Ischemic Stroke Upper Limb Recovery : Clinical, Neurophysiological and Radiological

March 2, 2025 updated by: Mohammad Ahmad Mohammad Korayem, Assiut University

Comparative Effectiveness of Ipsilesional High-frequency rTMS, Contralesional Continuous Burst Theta rTMS, and Sham rTMS, Each Combined With Physiotherapy, in Subacute Ischemic Stroke Upper Limb Recovery : Clinical, Neurophysiological and Radiological: A Double-blinded Randomized Clinical Trial

To compare the efficacy of lesional high-frequency rTMS, contralesional cTBS, and sham stimulation in improving motor and cognitive recovery in post-stroke patients undergoing physiotherapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Globally, stroke is the second leading cause of both death and disability. In 2020, the global prevalence of all stroke subtypes was 89.13 million cases, with acute ischemic stroke (AIS) comprising 76.47% of these, equating to 68.16 million cases . AIS presents a major global public health concern, given the wide range of disabilities it causes, including cognitive impairments. Survivors of stroke bear a significant burden due to the persistent disability they experience over time . Immediately following a stroke, motor impairments are accompanied by significant alterations in the affected primary motor cortex (M1) - detected by transcranial magnetic stimulation (TMS)- resulting in reduced cortical excitability. This can be evidenced by the absence of recordable motor evoked potentials (MEPs), diminished MEP amplitudes, and increased resting motor threshold (rMT). Additionally, stroke can alter brain connectivity, particularly in terms of functional connectivity, which has implications for recovery. Neuroplasticity plays a crucial role in recovery after stroke, allowing the brain to reorganize and compensate for lost functions. Physiotherapy is a cornerstone of post-stroke rehabilitation, particularly for upper limb recovery and cognitive improvement, with early intervention associated with better outcomes. Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the early stages post-stroke, enhancing motor and cognitive recovery, particularly when applied within two weeks of stroke onset. MEPs can be used to monitor changes in cortical excitability and have been linked to both cognitive and motor recovery. Combining rTMS with diffusion tensor imaging (DTI) allows for the assessment of both functional and structural brain changes, providing a deeper understanding of rTMS's therapeutic effects. DTI, through fractional anisotropy (FA), helps to evaluate white matter integrity, and studies have shown that increased FA correlates with motor recovery, making it a valuable tool in examining the structural changes induced by rTMS in stroke recovery. While high frequency rTMS targeting the ipsilesional motor cortex (M1) has demonstrated efficacy in enhancing motor recovery, contralesional continuous theta-burst stimulation (cTBS) has shown promising results offering an alternative by modulating interhemispheric inhibition. However, no studies have directly compared the efficacy of these two paradigms against each other and sham stimulation in subacute stroke recovery. This study seeks to address this gap by comparing the outcomes of lesional high frequency rTMS, contralesional cTBS, and sham stimulation in combination with physiotherapy.

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • First-ever ischemic stroke, confirmed by imaging.
  • Stroke affecting the non-dominant hemisphere (cortical or subcortical) within the middle cerebral artery (MCA) territory.
  • Acute to subacute stage of stroke (time since onset: 48 hours to 2 weeks).
  • Ability to comply with the study protocol and interventions.

Exclusion Criteria:

  • Hemorrhagic stroke or bilateral stroke.
  • Severe cognitive impairment, defined as a Montreal Cognitive Assessment (MoCA) score < 10.
  • Contraindications to TMS, such as: History of epilepsy, Metallic implants in the head, Other contraindications based on TMS safety guidelines.
  • Comorbid conditions that limit participation in rehabilitation.
  • Severe neglect or aphasia that would impede participation in therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ipsilesional high frequency rTMS combined with physiotherapy

rTMS Protocol:

Stimulation delivered to the hand area of the ipsilesional primary motor cortex (M1).

Frequency: 3 Hz.

Stimulation: 2 seconds per train, 37 trains per session.

Total pulses: 750 per session at 130% of the resting motor threshold (RMT).

Physiotherapy:

Patients receive standard physiotherapy sessions.
Device: Ipsilesional high frequency rTMS combined with physiotherapy
As mentioned in details in arms description.
Active Comparator: Contralesional Continuous Burst Theta rTMS (cTBS) + Physiotherapy

rTMS Protocol:

Stimulation delivered to the contralesional primary motor cortex (M1).

Protocol: Continuous bursts of 3 stimuli at 50 Hz, repeated at 5 bursts per second.

Duration: 40 seconds per session.

Stimulation intensity: 70% of RMT with a biphasic TMS-induced current at a 45° angle to the midline.

Physiotherapy:

Patients receive standard physiotherapy sessions.
Device: Contralesional Continuous Burst Theta rTMS (cTBS) + Physiotherapy
As mentioned in details in arms description.
Sham Comparator: Sham rTMS + Physiotherapy

Patients receive a sham stimulation designed to mimic rTMS without delivering active magnetic pulses.

This maintains blinding for participants and investigators.

Physiotherapy:

Patients receive standard physiotherapy sessions.
Device: Sham rTMS + Physiotherapy
As mentioned in details in arms description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Score in Nottingham Sensory Assessment in points
Time Frame: Within the time frame of the study , around 18 months
Within the time frame of the study , around 18 months
Score in modified Ashworth Scale in points
Time Frame: Within the time frame of the study , around 18 months
Within the time frame of the study , around 18 months
Score in Fugl-Meyer assessment scale in points
Time Frame: Within the time frame of the study , around 18 months
Within the time frame of the study , around 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortical Excitability Improvement
Time Frame: Within the time frame of the study , around 18 months
Evaluates changes in cortical excitability parameters (e.g., resting motor threshold measured in Percentage of maximum stimulator output , cortical silent period measured in milliseconds, transcallosal inhibition measured in milliseconds) using TMS after intervention.
Within the time frame of the study , around 18 months
Enhancement of White Matter Integrity
Time Frame: Within the time frame of the study , around 18 months
Assesses changes in white matter integrity using functional MRI.
Within the time frame of the study , around 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 15, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

January 15, 2025

First Submitted That Met QC Criteria

January 23, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 2, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NeuroRehabStroke2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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