An interventional study of High-frequency repetitive transcranial magnetic stimulation and Sham transcranial magnetic stimulation in Stroke and Upper Limb Paresis, sponsored by Ancor Rebassa Cabrera. Recruiting at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by Ancor Rebassa Cabrera · Not applicable, Interventional, and Basic science
The goal of this clinical trial is to learn if a single session of high-frequency repetitive transcranial magnetic stimulation (rTMS) can increase cortical motor activity in stroke patients with severe upper limb impairment.
The main question it aims to answer is:
Does one session of high-frequency rTMS increase the number of motor evoked potential (MEP)-positive points in the cortical motor map of the affected hemisphere compared to sham stimulation?
Researchers will compare high-frequency rTMS (10 Hz, 600 pulses) applied over the affected motor cortex to sham stimulation to see if rTMS increases detectable cortical motor responses in patients who have little or no voluntary hand movement after stroke.
Participants will:
Undergo a cortical motor mapping assessment before the intervention. Receive either one session of real rTMS or sham stimulation, depending on their randomly assigned group.
Undergo a second cortical motor mapping assessment immediately after the intervention.
Background Upper limb recovery is a top research priority in stroke rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising neuromodulation tool to enhance cortical excitability and promote motor recovery. However, most of the existing evidence is based on patients with detectable motor evoked potentials (MEP+) and mild-to-moderate impairment. Patients with MEP-negative status (MEP-) and severe upper limb deficits are systematically underrepresented in the literature, leaving a critical gap regarding the potential of rTMS in this subgroup.
The absence of MEP does not necessarily indicate complete structural damage to the corticospinal tract. Phenomena such as cerebral diaschisis - a transient suppression of cortical excitability in areas remote from the lesion - may render intact or partially intact pathways neurophysiologically silent. Cortical motor mapping with navigated TMS offers a more sensitive assessment than single-point MEP measurement, allowing evaluation of the spatial distribution and amplitude of cortical motor representations across a standardized grid.
Rationale High-frequency rTMS (10 Hz) applied over the ipsilesional primary motor cortex has been shown to increase cortical excitability and may reveal latent corticospinal tract activity in MEP-negative patients. This study proposes that a single session of high-frequency rTMS may shift some patients from MEP-negative to MEP-positive status, or increase the number of MEP-positive points in the cortical motor map, by transiently enhancing excitability in the affected hemisphere.
Study Design Prospective, single-centre, two-arm parallel-group randomized controlled trial conducted at the Neurorehabilitation Service of Hospital Sant Joan de Deu Palma (Mallorca, Spain). Participants are randomly assigned 1:1 to the intervention or control group using the REDCap randomisation module (simple randomisation). Analysis will be performed by intention-to-treat.
Intervention The intervention consists of a single session of high-frequency rTMS at 10 Hz applied using a Magstim Rapid2 stimulator (The Magstim Co. Ltd) with a D70mm Air Film figure-of-eight coil. A total of 600 pulses are delivered in trains of 15 pulses (1.5 s on, 10 s off) at an intensity of 80% of the motor threshold. The stimulation target is the optimal hotspot identified during the pre-intervention cortical motor mapping. In cases where no MEP-positive point is found, stimulation is applied at C3 or C4 (international 10-20 system), corresponding to the cortical motor representation of the affected hemisphere. The coil is placed at 45 degrees to the sagittal line with the handle pointing posteriorly. All parameters are within the safety guidelines established by the International Federation of Clinical Neurophysiology (IFCN).
The control group receives sham stimulation using the same coil rotated 90 degrees at the same position, producing comparable auditory and cutaneous sensations without effective cortical stimulation. This validated sham procedure controls for placebo and expectancy effects.
Cortical Motor Mapping Procedure Cortical motor mapping is performed before and immediately after the intervention in both groups. The procedure uses the Magstim Rapid2 stimulator with the D70mm Air Film coil and the Brainsight 2 neuronavigation software (Rogue Research Inc.), which reconstructs a 3D structural MRI brain model based on the MNI/Talairach standard space. A 5x5 grid with cells separated by 1 cm is centred on C3 or C4 of the affected hemisphere. Three biphasic pulses at 100% of the maximum stimulator output are delivered per grid point, with a 3-second inter-pulse interval.
Electromyographic responses are recorded using the UltraPro S100 system with Natus Elite Synergy software (Natus Medical Inc.) from the extensor carpi radialis muscle via bipolar surface Ag/AgCl electrodes placed according to SENIAM recommendations. Recording parameters: sampling frequency 5000 Hz, high-pass filter 1 Hz, low-pass filter 2000 Hz, notch filter 50 Hz, gain 1 mV/div, recording window -100 ms pre-stimulus to 300 ms post-stimulus. MEP amplitude is measured peak-to-peak; responses below 10 microvolts are assigned a value of 0.
Recruitment Participants are recruited from the Neurorehabilitation Service and referred by their rehabilitation physicians to the non-invasive brain neuromodulation unit. A neurophysiologist evaluates each candidate for contraindications and potential pharmacological interactions with TMS prior to enrolment. Written informed consent is obtained from all participants before any study procedure.
Safety Monitoring Immediately after completing the post-intervention mapping, participants complete an adverse events questionnaire based on IFCN safety guidelines, assessing pain, auditory changes, cutaneous sensations, muscle contractions, fatigue, drowsiness, mood changes, nausea, neck pain, anxiety, and concentration difficulties.
Statistical Analysis Sample size was calculated accepting an alpha risk of 0.05 and a statistical power above 0.80 in a bilateral contrast, requiring 27 subjects per group (54 total) to detect a statistically significant difference between two proportions (0 in the control group and 0.3 in the intervention group), using the Poisson approximation with an estimated 0% loss to follow-up.
The primary analysis will use repeated-measures ANOVA with group (intervention vs. control) and time (pre vs. post) as factors. Non-parametric tests (Wilcoxon, Friedman) will be applied where distributional assumptions are not met. Correlations between neurophysiological mapping variables and baseline clinical measures will be assessed using Pearson or Spearman coefficients depending on data distribution.
8,255 studies on the registry are indexed under Stroke; 2,056 are open to participants now.
This study's planned enrollment of 54 is above the median of 49 across 6,024 interventional studies indexed under Stroke.
Browse Stroke studies →This is the only study on the registry with Ancor Rebassa Cabrera as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
manual muscle testing score of 1 or less in finger extension.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive cortical motor mapping (pre-intervention), a single session of high-frequency rTMS over the affected motor cortex, and cortical motor mapping (post-intervention).
Device: High-frequency repetitive transcranial magnetic stimulation
Participants receive cortical motor mapping (pre-intervention), a single session of sham stimulation, and cortical motor mapping (post-intervention).
Device: Sham transcranial magnetic stimulation
Single session of 10 Hz rTMS using a Magstim Rapid2 stimulator with a D70mm Air Film figure-of-eight coil. Parameters: 600 pulses in trains of 15 pulses (1.5 s on, 10 s off) at 80% of the motor threshold over the optimal hotspot of the affected hemisphere (or C3/C4 if no MEP-positive point is identified). Parameters are within IFCN safety guidelines.
Same coil (Magstim Rapid2 / D70mm Air Film) placed at the same position as the active condition but rotated 90 degrees, producing comparable auditory and cutaneous sensations without effective cortical stimulation.
Number of MEP-positive points in the cortical motor map (Area)
Number of grid positions (5x5 grid, 1 cm spacing, centred on C3/C4 of the affected hemisphere) with a motor evoked potential amplitude of 10 microvolts or greater, recorded from the extensor carpi radialis muscle via surface EMG (UltraPro S100, Natus Medical Inc.) with navigated TMS (Brainsight 2, Rogue Research Inc.). Three biphasic pulses at 100% maximum stimulator output are applied per grid point.
Time frame: Immediately before and immediately after a single rTMS or sham session (same day)
Maximum MEP amplitude
Maximum peak-to-peak MEP amplitude (microvolts) recorded at any grid point of the cortical motor map.
Time frame: Immediately before and immediately after a single rTMS or sham session (same day)
Cortical map volume
Sum of all MEP amplitudes (microvolts) across all grid points of the cortical motor map.
Time frame: Immediately before and immediately after a single rTMS or sham session (same day)
Cortical map centre of gravity
Amplitude-weighted mean position (MNI/Talairach coordinates) of the cortical motor map, calculated by dividing the amplitude at each grid point by the total map volume.
Time frame: Immediately before and immediately after a single rTMS or sham session (same day)
Optimal hotspot coordinates
MNI/Talairach coordinates of the grid position yielding the highest MEP amplitude.
Time frame: Immediately before and immediately after a single rTMS or sham session (same day)
Fugl-Meyer Assessment - Upper Extremity (FMA-UE)
22-item ordinal scale assessing upper limb motor function post-stroke. Score range 0 to 66; higher scores indicate better motor function. Collected at baseline to explore correlations with neurophysiological mapping variables.
Time frame: Baseline (single assessment, same day as intervention)
Box and Block Test (BBT)
Manual dexterity test measuring the number of 2.5 cm wooden blocks transferred over a partition in 60 seconds. Higher scores indicate better manual dexterity. Collected at baseline to explore correlations with mapping variables.
Time frame: Baseline (single assessment, same day as intervention)
Wrist extension strength (dynamometry)
Isometric wrist extension force (kg) measured with a handheld dynamometer (MicroFet 2, Hoggan Industries). Mean of 3 trials recorded with the forearm supported.
Time frame: Baseline (single assessment, same day as intervention)
Wrist extension range of motion (goniometry)
Maximum passive wrist extension angle (degrees) measured with a standard goniometer.
Time frame: Baseline (single assessment, same day as intervention)
Plan to share: No — Individual participant data will not be shared. This is an investigator-initiated study with no external funding. Data will be stored according to Spanish and European data protection regulations (LOPDGDD, GDPR) and destroyed after 5 years following study completion.
Start is estimated for Sep 2026; primary completion for Dec 2026, 3 months later.
Of 3,108 non-industry interventional studies with no phase under Stroke, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 46. This study's planned 3 months is below that.
Counting every sponsor, half of 3,252 studies reached it within 23 months; a quarter within 10 and three quarters within 46.
How these figures are worked out, and which studies are left out of them.
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