NCT07567053

Brief Summary

This project examines the use of repetitive transcranial magnetic stimulation (rTMS) as a therapeutic approach to improve motor function in children with cerebral palsy (CP). By applying 6-Hz primed low and high-frequency rTMS and measuring brain responses through TMS-EEG, the study aims to enhance neural plasticity and motor recovery. The goal is to promote faster rehabilitation and reduce long-term healthcare needs.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
50mo left

Started May 2026

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

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

First Submitted

Initial submission to the registry

April 28, 2026

Completed
3 days until next milestone

Study Start

First participant enrolled

May 1, 2026

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 5, 2026

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2028

Expected
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2030

Last Updated

May 6, 2026

Status Verified

May 1, 2026

Enrollment Period

2 years

First QC Date

April 28, 2026

Last Update Submit

May 4, 2026

Conditions

Cerebral PalsyTypically Developing Children

Keywords

Cerebral PalsyCPTMSrepetitive Transcranial Magnetic StimulationTranscranial Magnetic StimulationrTMSTMS-EEG

Outcome Measures

Primary Outcomes (1)

  • Change on TMS-evoked potentials (TEPs)

    TEPs refer to the electrical responses in the brain elicited by rTMS. This technique involves applying magnetic pulses to specific brain areas, which induce electrical activity that can be recorded using EEG.

    Within the end of 4 weeks and 1-month follow-up of sham/real rTMS

Secondary Outcomes (1)

  • Change on cortical excitability - motor evoked potentials (MEPs)

    Within the end of 4 weeks and 1-month follow-up of sham/real rTMS

Other Outcomes (9)

  • Modified Ashworth Scale (MAS)

    Within the end of 4 weeks and 1-month follow-up of sham/real rTMS

  • Mirror Movement Assessment

    Within the end of 4 weeks and 1-month follow-up of sham/real rTMS

  • Gross Motor Function Measure (GMFM-88)

    Within the end of 4 weeks and 1-month follow-up of sham/real rTMS

  • +6 more other outcomes

Study Arms (4)

Intervention Group 1

EXPERIMENTAL

CP participants in the experiment intervention group 1 will receive rTMS using a figure-of-eight-shaped coil and rTMS stimulator (Nexstim, Finland) targeting the contralesional primary motor cortex. The intervention will consist of 10 sessions, each lasting 20 minutes, spread over four weeks. Each session will begin with priming: 10 minutes of 6-Hz rTMS at 90% of the resting motor threshold, delivered in two trains per minute (5 seconds per train with 25-second intervals between trains), totaling 600 priming pulses. This will be followed immediately by 10 minutes of 1-Hz rTMS at 90% of the resting motor threshold, delivered continuously without interruption, totaling 600 low-frequency pulses.

Device: MRIDevice: HD-EEG RecordingDevice: rTMS

Intervention Group 2

EXPERIMENTAL

CP Participants in experiment intervention group 2 will receive rTMS targeting the ipsilesional primary motor cortex. The intervention will consist of 10 sessions, each lasting 20 minutes, spread over four weeks. Each session will start with priming: 10 minutes of 6-Hz rTMS at 90% of the resting motor threshold, delivered in two trains per minute (5 seconds per train with 25-second intervals between trains), totaling 600 priming pulses. This will be followed immediately by 10 minutes of 10 Hz rTMS at 90% of the resting motor threshold, delivered continuously without interruption, totaling 2000 high-frequency pulses.

Device: MRIDevice: HD-EEG RecordingDevice: rTMS

Sham Group

SHAM COMPARATOR

CP participants in the sham group will receive sham rTMS by positioning the coil perpendicular to the scalp without delivering active stimulation, targeting both the contralesional and ipsilesional primary motor cortex. The intervention will consist of 10 sessions, each lasting 20 minutes, spread over four weeks.

Device: MRIDevice: HD-EEG RecordingDevice: rTMS

Control Group

ACTIVE COMPARATOR

Typically developed control group will complete a single baseline TMS-EEG session to measure TEPs. This involves high-density EEG recording during single-pulse TMS to assess cortical excitability. The session will last approximately 60-90 minutes.

Device: MRIDevice: HD-EEG Recording

Interventions

MRIDEVICE

All participants will undergo an MRI scan prior to the intervention to acquire T1-weighted images. MRI data will be provided by the Cook Children's Radiology Department. MRI scans will be used for neuronavigation.

Control GroupIntervention Group 1Intervention Group 2Sham Group
HD-EEG RecordingDEVICE

High-density EEG (HD-EEG) is a safe and non-invasive brain imaging technique. It involves placing a cap with small sensors on the child's head to measure the brain's electrical activity. This technique does not send any energy into the brain. The investigators will use the HD-EEG to measure motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs).

Control GroupIntervention Group 1Intervention Group 2Sham Group
rTMSDEVICE

rTMS is a safe, non-invasive way to map brain activity using gentle magnetic pulses. A small coil is placed near the head to stimulate nerve cells without any pain. This helps us understand how the brain controls movement.

Intervention Group 1Intervention Group 2Sham Group

Eligibility Criteria

Age6 Years - 18 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Aged 6 - 18 years,
  • A confirmed diagnosis of CP by a specialized professional (pediatric neurologist, PM\&R physician, neonatal developmental specialist, or neonatologist) is a prerequisite for participation,
  • Classified as high functioning (Level I, II, or III) according to the Gross Motor Function Classification System (GMFCS),
  • Age-appropriate ability to understand and comply with study procedure throughout the entire duration of the study,
  • Preserved vision and hearing (with or without correction).
  • Aged 6 - 18 years
  • Age-appropriate ability to understand and comply with study procedure throughout the entire duration of the study,
  • Preserved vision and hearing (with or without correction).

You may not qualify if:

  • Syndromic or genetic associations,
  • History of trauma or brain surgery,
  • Inability to remain still,
  • History of Epilepsy,
  • Severe coexisting sickness or illness unrelated to CP or unstable medical conditions such as pneumonia,
  • Modified Ashworth Scale: Shoulder, elbow, and wrist scores more than 3,
  • Limb contractures caused by injury,
  • Severe movement disorders that prevent intentional limb movements, such as choreoathetosis, or ballismus,
  • Any congenital brain abnormality shown on a traditional brain MRI,
  • A cast, splint, or recent surgery on the affected limb,
  • Botulinum toxin/phenol block applied to the afflicted limb within the last six months or anticipated during the research period,
  • Contraindications for rTMS include non-removable metallic objects close to a coil and implanted electronic devices, such as cochlear implants and pacemakers.
  • Syndromic or genetic associations,
  • History of trauma or brain surgery,
  • Inability to remain still,
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cook Children's Hospital

Fort Worth, Texas, 76107, United States

Location

Related Publications (62)

  • Mutanen, T. P., Biabani, M., Sarvas, J., Ilmoniemi, R. J. & Rogasch, N. C. Source-based artifact-rejection techniques available in TESA, an open-source TMS-EEG toolbox. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 13, 1349-1351 (2020)

    BACKGROUND

  • Rogasch, N. C. et al. Analysing concurrent transcranial magnetic stimulation and electroencephalographic data: A review and introduction to the open-source TESA software. Neuroimage 147, 934-951 (2017).

    BACKGROUND

  • Iversen, J. R. & Makeig, S. MEG/EEG data analysis using EEGLAB. Magnetoencephalography: From signals to dynamic cortical networks 391-406 (2019).

    BACKGROUND

  • Tadel, F., Baillet, S., Mosher, J. C., Pantazis, D. & Leahy, R. M. Brainstorm: A user-friendly application for MEG/EEG analysis. Comput Intell Neurosci 2011, 879716 (2011)

    BACKGROUND

  • Croarkin, P. E., Wall, C. A. & Lee, J. Applications of transcranial magnetic stimulation (TMS) in child and adolescent psychiatry. International Review of Psychiatry 23, 445-453 (2011).

    BACKGROUND

  • Gilbert, D. L. et al. Should transcranial magnetic stimulation research in children be considered minimal risk? Clinical neurophysiology 115, 1730-1739 (2004).

    BACKGROUND

  • Zewdie, E. et al. Safety and tolerability of transcranial magnetic and direct current stimulation in children: prospective single center evidence from 3.5 million stimulations. Brain Stimul 13, 565-575 (2020).

    BACKGROUND

  • Lerner, A. J., Wassermann, E. M. & Tamir, D. I. Seizures from transcranial magnetic stimulation 2012-2016: results of a survey of active laboratories and clinics. Clinical Neurophysiology 130, 1409-1416 (2019)

    BACKGROUND

  • Zewdie, E. et al. Safety and tolerability of transcranial magnetic and direct current stimulation in children: prospective single center evidence from 3.5 million stimulations. Brain Stimul 13, 565-575 (2020)

    BACKGROUND

  • Canadian Occupational Performance Measure (COPM) http://www.thecopm.ca/

    BACKGROUND

  • Jebsen-Taylor Hand Function Test (JHFT): http://www.strokengine.ca/assess/jhft/

    BACKGROUND

  • Melbourne Assessment of Unilateral Upper Limb Function (MUUL): Access can be found at http://www.rch.org.au/melbourneassessment/

    BACKGROUND

  • Assessment of Motor and Process Skills (AMPS): Access can be found at http://www.innovativeotsolutions.com/content/amps/

    BACKGROUND

  • Manual Ability Classification System (MACS) http://www.macs.nu/

    BACKGROUND

  • Krumlinde-Sundholm, L. & Eliasson, A.-C. Development of the Assisting Hand Assessment: a Rasch-built measure intended for children with unilateral upper limb impairments. Scand J Occup Ther 10, 16-26 (2003).

    BACKGROUND

  • Harb, A. & Kishner, S. Modified ashworth scale. in StatPearls [Internet] (StatPearls Publishing, 2023).

    BACKGROUND

  • Russell, D. J., Rosenbaum, P., Wright, M. & Avery, L. M. Gross Motor Function Measure (GMFM-66 & GMFM-88) Users Manual. (Mac keith press, 2002).

    BACKGROUND

  • Palisano, R. et al. Gross motor function classification system for cerebral palsy. Dev Med Child Neurol 39, 214-223 (1997).

    BACKGROUND

  • Jung, S. H., Shin, J. E., Jeong, Y. S. & Shin, H. I. Changes in motor cortical excitability induced by high-frequency repetitive transcranial magnetic stimulation of different stimulation durations. Clinical Neurophysiology 119, 71-79 (2008).

    BACKGROUND

  • Gillick, B. T. et al. Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: A randomized controlled trial. Dev Med Child Neurol 56, 44-52 (2014).

    BACKGROUND

  • Todd, G., Flavel, S. C. & Ridding, M. C. Priming theta-burst repetitive transcranial magnetic stimulation with low-and high-frequency stimulation. Exp Brain Res 195, 307-315 (2009).

    BACKGROUND

  • Carey, J. R., Anderson, D. C., Gillick, B. T., Whitford, M. & Pascual-Leone, A. 6-Hz primed low-frequency rTMS to contralesional M1 in two cases with middle cerebral artery stroke. Neurosci Lett 469, 338-342 (2010).

    BACKGROUND

  • Kakuda, W. et al. Application of combined 6-Hz primed low-frequency rTMS and intensive occupational therapy for upper limb hemiparesis after stroke. NeuroRehabilitation 29, 365-371 (2011).

    BACKGROUND

  • Tallabs, F. A. & Hammond-Tooke, G. D. Theta priming of 1-Hz rTMS in healthy volunteers: Effects on motor inhibition. Journal of Clinical Neurophysiology 30, 79-85 (2013).

    BACKGROUND

  • Cassidy, J. M. et al. A comparison of primed low-frequency repetitive transcranial magnetic stimulation treatments in chronic stroke. Brain Stimul 8, 1074-1084 (2015).

    BACKGROUND

  • Rajak, B. L., Gupta, M., Bhatia, D. & Mukherjee, A. Increasing Number of Therapy Sessions of Repetitive Transcranial Magnetic Stimulation Improves Motor Development by Reducing Muscle Spasticity in Cerebral Palsy Children. Ann Indian Acad Neurol 22, (2019).

    BACKGROUND

  • Lee, J. C. et al. Strategies for augmentation of high-frequency left-sided repetitive transcranial magnetic stimulation treatment of major depressive disorder. J Affect Disord 277, 964-969 (2020).

    BACKGROUND

  • Gupta, J. et al. Brain Stimulation and Constraint Induced Movement Therapy in Children With Unilateral Cerebral Palsy: A Randomized Controlled Trial. Neurorehabil Neural Repair 37, 266-276 (2023).

    BACKGROUND

  • Barr, M. S., Farzan, F., Davis, K. D., Fitzgerald, P. B. & Daskalakis, Z. J. Measuring GABAergic inhibitory activity with TMS-EEG and its potential clinical application for chronic pain. Journal of Neuroimmune Pharmacology 8, 535-546 (2013).

    BACKGROUND

  • Pellicciari, M. C., Veniero, D. & Miniussi, C. Characterizing the cortical oscillatory response to TMS pulse. Front Cell Neurosci 11, 38 (2017).

    BACKGROUND

  • Massimini, M., Tononi, G. & Huber, R. Slow waves, synaptic plasticity and information processing: insights from transcranial magnetic stimulation and high-density EEG experiments. European Journal of Neuroscience 29, 1761-1770 (2009).

    BACKGROUND

  • Ilmoniemi, R. J. & Kičić, D. Methodology for combined TMS and EEG. Brain Topogr 22, 233-248 (2010).

    BACKGROUND

  • Thut, G. & Pascual-Leone, A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr 22, 219-232 (2010).

    BACKGROUND

  • Daskalakis, Z. J., Farzan, F., Radhu, N. & Fitzgerald, P. B. Combined transcranial magnetic stimulation and electroencephalography: its past, present and future. Brain Res 1463, 93-107 (2012).

    BACKGROUND

  • Abraham, W. C. & Bear, M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci 19, 126-130 (1996).

    BACKGROUND

  • Kirton, A. Modeling developmental plasticity after perinatal stroke: defining central therapeutic targets in cerebral palsy. Pediatr Neurol 48, 81-94 (2013).

    BACKGROUND

  • Naeser, M. A. et al. Improved naming after TMS treatments in a chronic, global aphasia patient-case report. Neurocase 11, 182-193 (2005).

    BACKGROUND

  • Gupta, M., Rajak, B. L., Bhatia, D. & Mukherjee, A. Effect of repetitive transcranial magnetic stimulation on motor function and spasticity in spastic cerebral palsy. Int J Biomed Eng Technol 31, 365-374 (2019).

    BACKGROUND

  • Elbanna, S. T., Elshennawy, S. & Ayad, M. N. Noninvasive brain stimulation for rehabilitation of pediatric motor disorders following brain injury: systematic review of randomized controlled trials. Arch Phys Med Rehabil 100, 1945-1963 (2019).

    BACKGROUND

  • Casanova, M. F. et al. Effects of transcranial magnetic stimulation therapy on evoked and induced gamma oscillations in children with autism spectrum disorder. Brain Sci 10, 423 (2020).

    BACKGROUND

  • Pascual-Leone, A., Amedi, A., Fregni, F. & Merabet, L. B. The plastic human brain cortex. Annu. Rev. Neurosci. 28, 377-401 (2005).

    BACKGROUND

  • Chung, M. G. & Lo, W. D. Noninvasive brain stimulation: the potential for use in the rehabilitation of pediatric acquired brain injury. Arch Phys Med Rehabil 96, S129-S137 (2015).

    BACKGROUND

  • Chung, M. G. & Lo, W. D. Noninvasive brain stimulation: The potential for use in the rehabilitation of pediatric acquired brain injury. Archives of Physical Medicine and Rehabilitation vol. 96 S129-S137 Preprint at https://doi.org/10.1016/j.apmr.2014.10.013 (2015).

    BACKGROUND

  • Kirton, A. Advancing non-invasive neuromodulation clinical trials in children: Lessons from perinatal stroke. European Journal of Paediatric Neurology 21, 75-103 (2017).

    BACKGROUND

  • Hameed, M. et al. Transcranial Magnetic and Direct Current Stimulation in Children. Curr Neurol Neurosci Rep 17, (2017).

    BACKGROUND

  • Azizi, S. et al. The Impact of an Anti-Gravity Treadmill (AlterG) Training on Walking Capacity and Corticospinal Tract Structure in Children with Cerebral Palsy. Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference vol. 2017 (2017).

    BACKGROUND

  • Takeuchi, N., Oouchida, Y. & Izumi, S.-I. Motor control and neural plasticity through interhemispheric interactions. Neural Plast 2012, 823285 (2012).

    BACKGROUND

  • Cox, B. C., Cincotta, M. & Espay, A. J. Mirror movements in movement disorders: a review. Tremor and other hyperkinetic movements 2, (2012).

    BACKGROUND

  • Fling, B. W. & Seidler, R. D. Task-dependent effects of interhemispheric inhibition on motor control. Behavioural brain research 226, 211-217 (2012).

    BACKGROUND

  • Kuo, H., Ferre, C. L., Chin, K. Y., Friel, K. M. & Gordon, A. M. Mirror movements and brain pathology in children with unilateral cerebral palsy. Dev Med Child Neurol 65, 264-273 (2023).

    BACKGROUND

  • Yeargin-Allsopp, M. et al. Prevalence of cerebral palsy in 8-year-old children in three areas of the united states in 2002: A multisite collaboration. Pediatrics 121, 547-554 (2008).

    BACKGROUND

  • Stanley, F. J., Blair, E., Alberman, E. & Alberman, E. D. Cerebral Palsies: Epidemiology and Causal Pathways. (Cambridge University Press, 2000).

    BACKGROUND

  • Diego, A. & Leung, A. Transcranial direct current stimulation for improving gross motor function in children with cerebral palsy: A systematic review. British Journal of Occupational Therapy 83, 030802261989788 (2020).

    BACKGROUND

  • Bar-On, L. et al. Spasticity and its contribution to hypertonia in cerebral palsy. BioMed Research International vol. 2015 Preprint at https://doi.org/10.1155/2015/317047 (2015).

    BACKGROUND

  • Green, L. B. & Hurvitz, E. A. Cerebral Palsy. Phys Med Rehabil Clin N Am 18, 859-882 (2007).

    BACKGROUND

  • Reddihough, D. Cerebral Palsy in Childhood.

    BACKGROUND

  • Chen, X. J. & Li, S. C. Definition, classification and diagnostic conditions of cerebral palsy in children. Chinese Journal of Physical Medicine and Rehabilitation 29, 309 (2007).

    BACKGROUND

  • Hayes, C. Cerebral palsy: classification, diagnosis and challenges of care. British journal of nursing 19, 368-373 (2010).

    BACKGROUND

  • Colver, A., Fairhurst, C. & Pharoah, P. O. D. Cerebral palsy. in The Lancet vol. 383 1240-1249 (Elsevier B.V., 2014).

    BACKGROUND

  • Gupta, M., Rajak, B. L., Bhatia, D. & Mukherjee, A. Neuromodulatory effect of repetitive transcranial magnetic stimulation pulses on functional motor performances of spastic cerebral palsy children. J Med Eng Technol 42, 352-358 (2018).

    BACKGROUND

  • Sun, Y. Y. et al. Effects of repetitive transcranial magnetic stimulation on motor function and language ability in cerebral palsy: A systematic review and meta-analysis. Frontiers in Pediatrics vol. 11 Preprint at https://doi.org/10.3389/fped.2023.835472 (2023).

    BACKGROUND

  • Soleimani, F., Vameghi, R. & Biglarian, A. 213. Archives of Iranian Medicine vol. 16 (2013).

    BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, ChronicBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Christos Papadelis, PhD

    Cook Children's Health Care System

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Christos Papadelis, PhD

CONTACT

682-305-3236Christos.Papadelis@cookchilrens.org

Behnam Ghabel Damirchi, MSc

CONTACT

682-367-3956behnam.ghabeldamirchi@cookchildrens.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 28, 2026

First Posted

May 5, 2026

Study Start

May 1, 2026

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

June 1, 2030

Last Updated

May 6, 2026

Record last verified: 2026-05

Locations

US(1)