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NCT Number: NCT07073248

Effects of Intermitted Theta Burst Stimulation (iTBS) on Motor Recovery of Upper Extremity in Chronic Stroke Patients

This study aims to evaluate the effects and clinical feasibility of non-invasive brain stimulation protocols, specifically intermittent Theta Burst Stimulation, as part of rehabilitation interventions for motor recovery of upper extremity in the chronic phase after stroke.

It also seeks to explore the underlying mechanisms by investigating changes of functional and structural brain networks.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Rehabilitation Medicine, Danderyd Hospital, Danderyd, Stockholm 18288, Stockholm

Stockholm, Sweden

Location status: Recruiting

Location contact

Susanne Palmcrantz, PhD

CONTACT

[email protected]

004681235000

About this study

In this randomized controlled trial (RCT) group A will receive iTBS while group B will receive sham iTBS. Both groups will directly after the intervention receive 45 minutes of conventional physical therapy 3 times per week for 5 weeks, a total of 15 interventions by a blinded physiotherapist. For the iTBS intervention a Magstim Rapid² stimulator will be used also equipped with a Cadwell Sierra Summit EMG system [for motor evoked potential (MEP) measurements] and an ANT Visor2™ neuronavigation system [for navigated transcranial magnetic stimulation (TMS) interventions]. The iTBS parameters that will be used are: 600 pulses under 190 seconds at 80 % of Active Motor Threshold (AMT). The ipsilesional motor cortex will be targeted. The participants and clinical assessors will be blinded to the intervention.

All the patients will undergo advanced neuroimaging examinations before and after the intervention period. The exams will be then compared to identify neuroplastic changes in brain circuits.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age over 18
  • Chronic stroke (>6 months)
  • Residual hemiparesis FM-UE>17

Exclusion criteria

  • Metal implants
  • Epilepsy/seizures
  • Pregnancy
  • Claustrophobia (related to MRIs exams)
  • Severe cognitive impairment
  • Untreated or unstable depression/anxiety
  • Other disabilities prohibiting intensive physical training

Treatment and study plan

Intermittent Theta Burst Stimulation

Device

iTBS protocol: 600 pulses at 80% of AMT for 190 sec on the ipsilesional motor cortex, targeted with the support of a neuronavigational system, 15 sessions over a period of 5 weeks

Other names: iTBS, TMS

Sham Intermittent Theta Burst Stimulation

Device

It is identical to its active version, replicates operational sounds, and delivers a very shallow magnetic field to mimic the sensation of magnetic stimulation

Primary outcomes

  1. Fugl-Meyer Assessment - Upper Extremity

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    used to quantify recovery of sensorimotor function in the upper extremity after a stroke. It is a 63 item test scored on a 3-level ordinal scale. The score ranges from 0 to 126 points. A higher score indicates recovery of sensorimotor function.

Secondary outcomes

  1. Modified Ashworth Scale (MAS)

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    Assesses spasticity on a 6 point scale/muscle (0p no impairment, 5p max impairment/muscle)

  2. Neuroflexor

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    Medical technology device. Assesses spasticity by identifying the neural, viscous and elastic components during passive movement using a biomechanical algorithm (presented in Newton)

  3. Box and Block Test (BBT)

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    measures unilateral gross manual dexterity. The score is based on the number of blocks transferred from one compartment to the other compartment in 60 seconds. Higher scores indicate better manual dexterity.

  4. Action Research Arm Test (ARAT)

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    assesses upper extremity activity capacity in people with stroke. It is a 19-item test scored on a 4-level ordinal scale (0-3). The score ranges from 0 to 57. Higher scores indicate better performance of the upper extremity.

  5. Dextrain Manipulandum™

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    allows measurement of flexion-extension finger movements. Force sensors are incorporated in the ergonomically designed tool allowing precision measurement of finger movements. The tool is coupled with specific exercises for evaluation of key components of manual dexterity.

  6. Hand-held Dynamometer/Grip Strength

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    A quantitative and objective measure of isometric muscular strength of the hand and forearm. This instrument is scored using force production: kilograms or pounds. Maximum grip is the mean of three trials.

  7. Purdue Pegboard Test (PPT)

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    is a test of fingertip dexterity and gross movement of the hand, fingers and arm in patients with impairments of the upper extremity resulting from neurological and musculoskeletal conditions. Number of correctly placed pinns within a time frame are counted and a higher scores indicate better dexterity.

  8. Visuomotor force tracking

    Time frame: At baseline and after completion of the 5 week intervention and at the 12 weeks follow up, to assess changes

    Subjects perform a visually guided, isometric precision grip ramp-and-hold force-tracking task by holding a manipulandum. The standardized visuomotor ramp-and-hold task is performed by following the target force with a cursor on a screen as precisely as possible.

  9. Montreal Cognitive Assessment (MoCA)

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    Assesses mental function (0p max impairment summed up to 30p no detected impairment)

  10. Canadian Occupational Performance Measure

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    Capture the participant´s perception of performance in everyday living and will be used to set goals for the intervention.

  11. Stroke Impact Scale (SIS)

    Time frame: At baseline and after completion of the 5 week intervention and at the 12 weeks follow up, to assess changes

    is a self-report questionnaire that evaluates disability and health-related quality of life after stroke. It has 8 domains: strength, hand function, mobility, physical and instrumental activities of daily living (ADL and IADL), memory and thinking, communication, emotion, and social participation. It uses a 5-point Likert scale to assess the difficulty of performing various tasks within each domain. Higher scores indicate better outcome.

  12. Motor Evoked Potentials (MEPs)

    Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.

    electrical signals recorded from neural tissue or muscle following activation of central motor pathways. MEPs assess the integrity of descending motor pathways.

  13. Resting state functional MRI (rs-fMRI)

    Time frame: At baseline and after completion of the 5 week intervention to assess changes.

    a method aimed at examining intrinsic networks in the brain while no task is performed (rest); this is to estimate correlations between brain regions.

  14. Diffusion Tension Imaging (DTI)

    Time frame: At baseline and after completion of the 5 week intervention to assess changes.

    a method aimed at mapping structural correlations between brain regions.

Other outcomes

  1. National Institutes of Health Stroke Scale (NIHSS)

    Time frame: At baseline

    quantifies stroke severity based on weighted evaluation findings. The total NIHSS score ranges from 0 to 42, with higher scores indicating more severe strokes, categorized as follows: minor stroke (1-4), moderate stroke (5-15), moderate to severe stroke (16-20), and severe stroke (21-42).

  2. Barthel Index (BI)

    Time frame: At baseline.

    measures a person's ability to complete activities of daily living (ADL). Scores range from 0 to 100, categorized as follows: Total dependence (0-20), Severe dependence (21-60), Moderate dependence (61-90), Slight dependence (91-99), and Independence (100).

  3. Theoretical Framework of Acceptability questionnaire

    Time frame: After completion of the 5 week intervention to assess acceptability.

    to assess the acceptability of healthcare interventions, based on the developed Theoretical Framework of Acceptability (TFA). It uses a 5-point Likert scale to assess acceptability of the intervention. Higher scores indicate higher acceptability.

Study contacts

Contact information is provided by the study sponsor or research team.

Susanne Palmcrantz, PhD, Associate Professor

CONTACT

[email protected]

004681235000

Sponsors and collaborators

Lead sponsor

Danderyd Hospital

Other

Collaborators

  • Karolinska Institutet

Registry information

Official study title

Neuroplastic Changes and Effects of Intermittent Theta Burst Stimulation (iTBS) on Motor Recovery of Upper and Lower Extremity in Chronic Stroke Patients

Acronym: NIMBLE

Important dates

Study start
2025
Primary completion
2030
Study completion
2030
First posted
Jul 18, 2025
Registry last updated
Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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