Spinal Cord Injuries (SCI)NCT07586644
Combined rTMS and tSCS for Upper Limb Recovery in Cervical SCI
A study testing Transcranial Magnetic Stimulation and Transcutaneous Spinal Cord Stimulation in people with Spinal Cord Injuries (SCI), run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
This clinical trial investigates whether combining cortical and spinal neuromodulation can improve upper limb motor recovery in adults with chronic incomplete cervical spinal cord injury (SCI). Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Spinal Cord Injuries (SCI)
- What is being tested?
- Transcranial Magnetic Stimulation and Transcutaneous Spinal Cord Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSingapore
- Study dates
- 30 Mar 2027to 30 Dec 2028
- Phase
- Interventional
- 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronicity: More than 12 months post-injury at enrollment
- Injury type: Traumatic or non-traumatic incomplete cervical SCI, neurological level C2 to C8
- AIS classification: Grade C or D
- UEMS: 10 to 20 out of 25 on the more impaired side; lower bound 10 ensures sufficient voluntary activation for task training and elicitable MEPs, upper bound avoids ceiling effects.
- Grip strength: MMT grade 3 or higher in finger flexors (C8 myotome) on at least one side.
- Hand function: Able to transfer at least 1 block across the partition within 60 seconds on the more impaired side.
Show all 11Show fewer
- Sitting tolerance: Able to tolerate upright seated posture in own wheelchair for at least 1 continuous hour without symptomatic orthostatic hypotension or pressure-related discomfort requiring position change.
- Medical stability: No acute medical complications
- Informed consent: Able to provide written informed consent and comply with the study schedule
- Medications: Stable regimen for 4 weeks prior, AND participant plus clinician agreement that dosage (baclofen, tizanidine, botulinum toxin) remains unchanged throughout the 12-week intervention; any change logged as protocol deviation
- Surgical clearance: Cleared by neurosurgeon or orthopedic surgeon for participation in tSCS-based rehabilitation
Who cannot join
- Seizure history: History of seizures or epilepsy
- Implanted devices: Intracranial metallic implants, cochlear implants, cardiac pacemakers, or other implanted electronic devices. Cervical spinal instrumentation (e.g., posterior rods, plates, or screws at C2 to T1) is not an exclusion for tSCS provided overlying skin is intact; participants with hardware directly beneath planned electrode sites will undergo low-intensity test stimulation during screening, and electrode placement will be shifted by one interspace if current distortion, focal discomfort, or unexpected motor thresholds are observed. Intracranial hardware remains an absolute exclusion for iTBS.
- Prior craniotomy: Prior neurosurgical procedure involving craniotomy
- Pregnancy: Currently pregnant or intending to become pregnant during the study period
- Psychiatric or cognitive: Active psychiatric illness (eg, untreated major depression, psychosis) or cognitive impairment precluding informed consent
- Concurrent neurological disease: Progressive or degenerative neurological condition (eg, multiple sclerosis, motor neuron disease)
Show all 10Show fewer
- Concurrent trials: Participation in another interventional rehabilitation or neurostimulation trial
- Skin integrity: Skin lesions or breakdown at electrode placement sites (scalp or posterior cervical spine)
- Cortical excitability medications: Medications known to alter cortical excitability (eg, antiepileptic drugs, high-dose benzodiazepines) that cannot be stabilized for at least 2 weeks prior to enrollment
- Severe spasticity: Modified Tardieu Scale muscle reaction grade 4 (unfatigable clonus >10 s) at elbow or wrist flexors on the more impaired side, or spasticity judged by the treating physician as unresponsive to optimised pharmacological management.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Tang Ning, PhD contact
Singapore1 site
Alexandra Hospital/ National University Hospital
Singapore
Gobinathan Chandran, +65 94575924, gobinathan_chandran@nuhs.edu.sg
About this study
Official title: Combined Repetitive Transcranial Magnetic Stimulation and Transcutaneous Spinal Cord Stimulation for Upper Limb Recovery in Chronic Incomplete Cervical Spinal Cord Injury: Pilot Randomized Controlled Trial
This clinical trial investigates whether combining cortical and spinal neuromodulation can improve upper limb motor recovery in adults with chronic incomplete cervical spinal cord injury (SCI). Restoring upper limb function is the top rehabilitation priority for individuals with tetraplegia, yet effective interventions remain limited.
The study combines transcutaneous spinal cord stimulation (tSCS), which enhances spinal circuit excitability, with intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation that increases cortical excitability and strengthens descending motor pathways. While each approach has shown independent promise, their combined use has not been evaluated in a controlled trial.
Read more
Eligible participants are adults aged 21-65 with chronic (>12 months post-injury) incomplete cervical SCI (ASIA Impairment Scale grade C or D, levels C2-C8). A total of 24 participants will be randomised 1:1 to either combined iTBS and tSCS plus standardised upper limb rehabilitation, or tSCS plus rehabilitation alone, across 24 sessions over 12 weeks.
The primary outcome is change in Upper Extremity Motor Score from baseline to week 12. Secondary outcomes cover functional performance, independence, spasticity, corticospinal excitability, quality of life, and goal attainment. Assessments occur at baseline, post-intervention, and at 4- and 12-week follow-up.
As a pilot randomised controlled trial, this study will generate the first controlled evidence on adjunctive cortical neuromodulation alongside tSCS-based rehabilitation, while also producing feasibility data to inform the design of a future definitive multicentre trial.
Read the detailed description
Background: Cervical spinal cord injury (SCI) results in severe upper limb impairment, with restoration of hand and arm function ranked as the highest rehabilitation priority by individuals with tetraplegia. Transcutaneous spinal cord stimulation (tSCS) has emerged as a promising approach for enhancing upper limb recovery. Intermittent theta burst stimulation (iTBS), an efficient form of repetitive transcranial magnetic stimulation, can enhance cortical excitability and descending motor drive. However, the benefit of combining these complementary neuromodulation modalities to simultaneously target supraspinal and spinal circuits has not been evaluated in a controlled trial.
Objective: This study aims to evaluate the feasibility, safety, and preliminary efficacy of combined cortical neuromodulation (iTBS) and spinal neuromodulation (tSCS) versus tSCS alone, each paired with standardized upper limb rehabilitation, for improving upper limb motor function in chronic incomplete cervical SCI.
Methods: This single-center, two-arm, assessor-blinded, pilot randomized controlled trial will enroll 24 adults aged 21 to 65 years with chronic (more than 12 months post-injury) incomplete cervical SCI (American Spinal Injury Association Impairment Scale grade C or D, neurological level C2 to C8). Participants will be randomized 1:1 to receive either iTBS combined with tSCS plus standardized upper limb rehabilitation or tSCS plus upper limb rehabilitation alone. Interventions will be delivered twice weekly for 12 weeks (24 sessions). The primary outcome is the change in Upper Extremity Motor Score from baseline to 12 weeks. Secondary outcomes include measures of upper limb function, independence, spasticity, corticospinal excitability, quality of life, and goal attainment. Assessments will be conducted at baseline, post-intervention, and at 4-week and 12-week follow-up.
Conclusions: This pilot trial will provide the first controlled evidence on whether adjunctive cortical neuromodulation via iTBS produces additional upper limb motor recovery beyond tSCS-based rehabilitation in chronic incomplete cervical SCI. Feasibility data and effect size estimates will inform the design of a subsequent multicenter confirmatory trial.
- Conditions
- Spinal Cord Injuries (SCI)
- Being tested
- Transcranial Magnetic Stimulation, Transcutaneous Spinal Cord Stimulation
- Keywords
- transcutaneous spinal cord stimulation, intermittent theta burst stimulation, repetitive transcranial magnetic stimulation, cervical spinal cord injury, upper limb rehabilitation, neuromodulation, convergent neuromodulation, tetraplegia
- Medical subject headings
- Spinal Cord Injuries, Quadriplegia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that enhances cortical excitability and corticospinal drive. Intermittent theta burst stimulation (iTBS), a brief patterned form of rTMS, produces lasting facilitatory effects and is more time-efficient. Evidence indicates rTMS improves motor function, reduces spasticity, and enhances neuroplasticity in SCI.
Transcutaneous Spinal Cord StimulationDevice
Transcutaneous spinal cord stimulation (tSCS) is a non-invasive neuromodulation technique that delivers electrical stimulation over the spine to activate sensory afferents and enhance spinal motor circuit excitability. Early studies showed it can enable voluntary movement even in motor-complete spinal cord injury (SCI), with subsequent research demonstrating improvements in motor function, standing, and walking in incomplete SCI. Evidence suggests tSCS modulates both spinal and corticospinal pathways, supporting neuroplasticity. The Up-LIFT trial (2024) provided strong clinical evidence, showing that tSCS combined with rehabilitation significantly improved upper limb strength and function in chronic cervical SCI, with 72% of participants meeting effectiveness endpoints and no serious adverse events. Later studies confirmed its safety in home and community settings, though standardization and larger trials remain needed.
| Study group | Role | What they receive |
|---|---|---|
| iTBS combined with tSCS plus standardized upper limb rehabilitation | Experimental | Interventions are delivered twice weekly for 12 weeks (24 sessions): iTBS over M1 followed by combined tSCS plus upper limb rehabilitation (45-60 min).
tSCS uses a constant-current stimulator with 5×10 cm electrodes at C3-C4 and/or C6-C7, with reference electrodes over the ASIS or clavicles. Parameters: biphasic pulses at 30 Hz, 1 ms pulses with 10 kHz carrier frequency, intensity 40-120 mA, delivered continuously for ~45 minutes.
iTBS is delivered over the M1 hand area contralateral to the more impaired limb. Protocol: 600 pulses (3-pulse bursts at 50 Hz, repeated at 5 Hz, 80% AMT over 3-4 minutes.
Upper limb rehabilitation follows immediately, supervised by a physiotherapist and occupational therapist, based on the Up-LIFT trial protocol. Sessions include reaching, finger movements, pinch, grip, bimanual coordination, and individualised functional tasks, with difficulty progressed systematically. Receives: Device: Transcranial Magnetic Stimulation; Device: Transcutaneous Spinal Cord Stimulation |
| tSCS plus standardized upper limb rehabilitation only | Active comparator | Interventions are delivered twice weekly for 12 weeks (24 sessions).
tSCS uses a constant-current stimulator with 5×10 cm electrodes at C3-C4 and/or C6-C7, with reference electrodes over the ASIS or clavicles. Parameters: biphasic pulses at 30 Hz, 1 ms pulses with 10 kHz carrier frequency, intensity 40-120 mA, delivered continuously for ~45 minutes. The carrier frequency reduces skin discomfort and enables deeper dorsal root activation.
Upper limb rehabilitation follows immediately, supervised by a physiotherapist and occupational therapist, based on the Up-LIFT trial protocol. Sessions include reaching, finger movements, pinch, grip, bimanual coordination, and individualised functional tasks, with difficulty progressed systematically. Receives: Device: Transcutaneous Spinal Cord Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Upper Extremity Motor Score (UEMS)
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Measured: Week 0
Upper Extremity Motor Score (UEMS)
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Measured: Week 12
Upper Extremity Motor Score (UEMS)
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Measured: Week 16
Upper Extremity Motor Score (UEMS)
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Measured: Week 24
Secondary outcomes (44)
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
The GRASSP V2 is an assessment for tetraplegia, typically scored across 5 specific subtests rather than a single total sum. Key maximum scores for GRASSP V2 include 50 for Strength (10 muscles x 5), 12 for Dorsal Sensation, 12 for Palmar Sensation, and 30 for Prehension Performance. A higher score indicates better outcomes.
Measured: Week 0
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
The GRASSP V2 is an assessment for tetraplegia, typically scored across 5 specific subtests rather than a single total sum. Key maximum scores for GRASSP V2 include 50 for Strength (10 muscles x 5), 12 for Dorsal Sensation, 12 for Palmar Sensation, and 30 for Prehension Performance. A higher score indicates better outcomes.
Measured: Week 12
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
The GRASSP V2 is an assessment for tetraplegia, typically scored across 5 specific subtests rather than a single total sum. Key maximum scores for GRASSP V2 include 50 for Strength (10 muscles x 5), 12 for Dorsal Sensation, 12 for Palmar Sensation, and 30 for Prehension Performance. A higher score indicates better outcomes.
Measured: Week 16
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
The GRASSP V2 is an assessment for tetraplegia, typically scored across 5 specific subtests rather than a single total sum. Key maximum scores for GRASSP V2 include 50 for Strength (10 muscles x 5), 12 for Dorsal Sensation, 12 for Palmar Sensation, and 30 for Prehension Performance. A higher score indicates better outcomes.
Measured: Week 24
Grip/Pinch Strength
Maximal grip force (Jamar dynamometer), lateral pinch, tip pinch, and tripod pinch (pinch gauge)
Measured: Week 0
Grip/Pinch Strength
Maximal grip force (Jamar dynamometer), lateral pinch, tip pinch, and tripod pinch (pinch gauge)
Measured: Week 12
Grip/Pinch Strength
Maximal grip force (Jamar dynamometer), lateral pinch, tip pinch, and tripod pinch (pinch gauge)
Measured: Week 16
Grip/Pinch Strength
Maximal grip force (Jamar dynamometer), lateral pinch, tip pinch, and tripod pinch (pinch gauge)
Measured: Week 24
Nine-Hole Peg Test
Timed fine motor dexterity assessment. The participant is instructed to pick up the pegs one by one and place them into the holes as fast as possible. Once all pegs are in the holes, the participant immediately removes them one by one and returns them to the container, as fast as possible. The primary score is the number of seconds taken to complete the task. Shorter times indicate better fine manual dexterity.
Measured: Week 0
Nine-Hole Peg Test
Timed fine motor dexterity assessment. The participant is instructed to pick up the pegs one by one and place them into the holes as fast as possible. Once all pegs are in the holes, the participant immediately removes them one by one and returns them to the container, as fast as possible. The primary score is the number of seconds taken to complete the task. Shorter times indicate better fine manual dexterity.t
Measured: Week 12
Nine-Hole Peg Test
Timed fine motor dexterity assessment. The participant is instructed to pick up the pegs one by one and place them into the holes as fast as possible. Once all pegs are in the holes, the participant immediately removes them one by one and returns them to the container, as fast as possible. The primary score is the number of seconds taken to complete the task. Shorter times indicate better fine manual dexterity.
Measured: Week 16
Nine-Hole Peg Test
Timed fine motor dexterity assessment. The participant is instructed to pick up the pegs one by one and place them into the holes as fast as possible. Once all pegs are in the holes, the participant immediately removes them one by one and returns them to the container, as fast as possible. The primary score is the number of seconds taken to complete the task. Shorter times indicate better fine manual dexterity.
Measured: Week 24
Box and Block Test
Gross manual dexterity (number of blocks transferred in 60 seconds)
Measured: Week 0
Box and Block Test
Gross manual dexterity (number of blocks transferred in 60 seconds)
Measured: Week 12
Box and Block Test
Gross manual dexterity (number of blocks transferred in 60 seconds)
Measured: Week 16
Box and Block Test
Gross manual dexterity (number of blocks transferred in 60 seconds)
Measured: Week 24
Capabilities of Upper Extremity Test (CUE-T)
CUE-T is a standardized, performance-based assessment tool designed specifically to measure functional limitations in the arms and hands of individuals with tetraplegia due to SCI. It objectively evaluates how well a person can perform basic and instrumental ADLs, such as reaching, grasping, and manipulating objects. Higher score indicates better outcome.
Measured: Week 0
Capabilities of Upper Extremity Test (CUE-T)
CUE-T is a standardized, performance-based assessment tool designed specifically to measure functional limitations in the arms and hands of individuals with tetraplegia due to SCI. It objectively evaluates how well a person can perform basic and instrumental ADLs, such as reaching, grasping, and manipulating objects. Higher score indicates better outcome.
Measured: Week 12
Capabilities of Upper Extremity Test (CUE-T)
CUE-T is a standardized, performance-based assessment tool designed specifically to measure functional limitations in the arms and hands of individuals with tetraplegia due to SCI. It objectively evaluates how well a person can perform basic and instrumental ADLs, such as reaching, grasping, and manipulating objects. Higher score indicates better outcome.
Measured: Week 16
Capabilities of Upper Extremity Test (CUE-T)
CUE-T is a standardized, performance-based assessment tool designed specifically to measure functional limitations in the arms and hands of individuals with tetraplegia due to SCI. It objectively evaluates how well a person can perform basic and instrumental ADLs, such as reaching, grasping, and manipulating objects. Higher score indicates better outcome.
Measured: Week 24
Spinal Cord Independence Measure III (SCIM-III)
It measures independence in daily activities across three main domains-Self-Care, Respiration/Sphincter Management, and Mobility-with a total score ranging from 0 to 100. Higher score indicates better outcome.
Measured: Week 0
Spinal Cord Independence Measure III (SCIM-III)
It measures independence in daily activities across three main domains-Self-Care, Respiration/Sphincter Management, and Mobility-with a total score ranging from 0 to 100. Higher score indicates better outcome.
Measured: Week 12
Spinal Cord Independence Measure III (SCIM-III)
It measures independence in daily activities across three main domains-Self-Care, Respiration/Sphincter Management, and Mobility-with a total score ranging from 0 to 100. Higher score indicates better outcome.
Measured: Week 16
Spinal Cord Independence Measure III (SCIM-III)
It measures independence in daily activities across three main domains-Self-Care, Respiration/Sphincter Management, and Mobility-with a total score ranging from 0 to 100. Higher score indicates better outcome.
Measured: Week 24
R2-R1 in Modified Tardieu Scale
Modified Tardieu Scale measures velocity-dependent spasticity of elbow and wrist flexors/extensors. R1 (Angle of Catch) is measured during the fast (V3) stretch, indicating when the spastic reflex is triggered. R2 (Full Range of Motion) is measured during the slow (V1) stretch, indicating the maximum joint angle. A lower R2-R1 value is better (indicating less spasticity and more normal muscle behaviour).
Measured: Week 0
R2-R1 in Modified Tardieu Scale
Modified Tardieu Scale measures velocity-dependent spasticity of elbow and wrist flexors/extensors. R1 (Angle of Catch) is measured during the fast (V3) stretch, indicating when the spastic reflex is triggered. R2 (Full Range of Motion) is measured during the slow (V1) stretch, indicating the maximum joint angle. A lower R2-R1 value is better (indicating less spasticity and more normal muscle behaviour).
Measured: Week 6
R2-R1 in Modified Tardieu Scale
Modified Tardieu Scale measures velocity-dependent spasticity of elbow and wrist flexors/extensors. R1 (Angle of Catch) is measured during the fast (V3) stretch, indicating when the spastic reflex is triggered. R2 (Full Range of Motion) is measured during the slow (V1) stretch, indicating the maximum joint angle. A lower R2-R1 value is better (indicating less spasticity and more normal muscle behaviour).
Measured: Week 12
R2-R1 in Modified Tardieu Scale
Modified Tardieu Scale measures velocity-dependent spasticity of elbow and wrist flexors/extensors. R1 (Angle of Catch) is measured during the fast (V3) stretch, indicating when the spastic reflex is triggered. R2 (Full Range of Motion) is measured during the slow (V1) stretch, indicating the maximum joint angle. A lower R2-R1 value is better (indicating less spasticity and more normal muscle behaviour).
Measured: Week 16
R2-R1 in Modified Tardieu Scale
Modified Tardieu Scale measures velocity-dependent spasticity of elbow and wrist flexors/extensors. R1 (Angle of Catch) is measured during the fast (V3) stretch, indicating when the spastic reflex is triggered. R2 (Full Range of Motion) is measured during the slow (V1) stretch, indicating the maximum joint angle. A lower R2-R1 value is better (indicating less spasticity and more normal muscle behaviour).
Measured: Week 24
Central Motor Conduction Time (CMCT)
It evaluates the integrity of the corticospinal tract by subtracting peripheral motor conduction time from the total Motor Evoked Potential (MEP). As per IFCN guidelines: CMCT = MEP latency minus PCT, where PCT = (F-latency + M-latency minus 1) / 2. A shorter CMCT indicates better outcome.
Measured: Week 0
Central Motor Conduction Time (CMCT)
It evaluates the integrity of the corticospinal tract by subtracting peripheral motor conduction time from the total Motor Evoked Potential (MEP). As per IFCN guidelines: CMCT = MEP latency minus PCT, where PCT = (F-latency + M-latency minus 1) / 2. A shorter CMCT indicates better outcome.
Measured: Week 12
Central Motor Conduction Time (CMCT)
It evaluates the integrity of the corticospinal tract by subtracting peripheral motor conduction time from the total Motor Evoked Potential (MEP). As per IFCN guidelines: CMCT = MEP latency minus PCT, where PCT = (F-latency + M-latency minus 1) / 2. A shorter CMCT indicates better outcome.
Measured: Week 16
Central Motor Conduction Time (CMCT)
It evaluates the integrity of the corticospinal tract by subtracting peripheral motor conduction time from the total Motor Evoked Potential (MEP). As per IFCN guidelines: CMCT = MEP latency minus PCT, where PCT = (F-latency + M-latency minus 1) / 2. A shorter CMCT indicates better outcome.
Measured: Week 24
peak-to-peak amplitude of motor evoked potential (MEP)
Measured by transcranial magnetic stimulation (TMS). Amplitude, latency, resting and active motor thresholds from FDI and APB will be recorded. The bigger value of peak-to peak amplitude of MEP indicates better outcome
Measured: Week 0
peak-to-peak amplitude of motor evoked potential (MEP)
Measured by transcranial magnetic stimulation (TMS). Amplitude, latency, resting and active motor thresholds from FDI and APB will be recorded. The bigger value of peak-to peak amplitude of MEP indicates better outcome
Measured: Week 12
peak-to-peak amplitude of motor evoked potential (MEP)
Measured by transcranial magnetic stimulation (TMS). Amplitude, latency, resting and active motor thresholds from FDI and APB will be recorded. The bigger value of peak-to peak amplitude of MEP indicates better outcomes.
Measured: Week 16
peak-to-peak amplitude of motor evoked potential (MEP)
Measured by transcranial magnetic stimulation (TMS). Amplitude, latency, resting and active motor thresholds from FDI and APB will be recorded. The bigger value of peak-to peak amplitude of MEP indicates better outcome
Measured: Week 24
EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
The EQ-5D-5L is a standardized, self-reported questionnaire used to measure health-related quality of life (HRQoL) across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension scores from 1 to5, with higher score indicating worse outcome.
Measured: Week 0
EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
The EQ-5D-5L is a standardized, self-reported questionnaire used to measure health-related quality of life (HRQoL) across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension scores from 1 to5, with higher score indicating worse outcome.
Measured: Week 12
EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
The EQ-5D-5L is a standardized, self-reported questionnaire used to measure health-related quality of life (HRQoL) across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension scores from 1 to5, with higher score indicating worse outcome.
Measured: Week 24
Modified goal attainment scale (GAS)
Patient-identified goals scored on a standardized attainment scale. Generally, a higher score indicates a better outcome.
Measured: Week 0
Modified goal attainment scale (GAS)
Patient-identified goals scored on a standardized attainment scale. Generally, a higher score indicates a better outcome.
Measured: Week 12
Modified goal attainment scale (GAS)
Patient-identified goals scored on a standardized attainment scale. Generally, a higher score indicates a better outcome.
Measured: Week 16
Modified goal attainment scale (GAS)
Patient-identified goals scored on a standardized attainment scale. Generally, a higher score indicates a better outcome.
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2026
- Study start30 Mar 2027 (estimated)
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord Injuries (SCI)Studies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center, two-arm, assessor-blinded, pilot randomized controlled trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gobinathan Chandran, MBBS, Principal investigator, NUH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07586644
- Sponsor's protocol ID
- 1833493
- Status last verified
- Apr 2026
- First submitted
- 8 May 2026
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: According to institution research polices, research agreement needs to be signed before sharing individual data with external parties.
Publications
Shankar R, Tang N, Chandran G. Combined repetitive transcranial magnetic stimulation and transcutaneous spinal cord stimulation for upper limb recovery in chronic incomplete cervical spinal cord injury: protocol for a pilot randomized controlled trial. Front Neurosci. 2026 May 28;20:1833493. doi: 10.3389/fnins.2026.1833493. eCollection 2026.
PubMed 42292339
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Repetitive Transcranial Magnetic Stimulation and Transcutaneous Spinal Cord Stimulation for Upper Limb Recovery in Chronic Incomplete Cervical Spinal Cord Injury: Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07586644
- Acronym / sponsor ID
- 1833493
- Conditions
- Spinal Cord Injuries (SCI)
- Keywords
- transcutaneous spinal cord stimulation, intermittent theta burst stimulation, repetitive transcranial magnetic stimulation, cervical spinal cord injury, upper limb rehabilitation, neuromodulation, convergent neuromodulation, tetraplegia
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 30 Mar 2027 (estimated)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 14 May 2026 (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.
This clinical trial investigates whether combining cortical and spinal neuromodulation can improve upper limb motor recovery in adults with chronic incomplete cervical spinal cord injury (SCI). Restoring upper limb function is the top rehabilitation priority for individuals with tetraplegia, yet effective interventions remain limited.
The study combines transcutaneous spinal cord stimulation (tSCS), which enhances spinal circuit excitability, with intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation that increases cortical excitability and strengthens descending motor pathways. While each approach has shown independent promise, their combined use has not been evaluated in a controlled trial.
Eligible participants are adults aged 21-65 with chronic (>12 months post-injury) incomplete cervical SCI (ASIA Impairment Scale grade C or D, levels C2-C8). A total of 24 participants will be randomised 1:1 to either combined iTBS and tSCS plus standardised upper limb rehabilitation, or tSCS plus rehabilitation alone, across 24 sessions over 12 weeks.
The primary outcome is change in Upper Extremity Motor Score from baseline to week 12. Secondary outcomes cover functional performance, independence, spasticity, corticospinal excitability, quality of life, and goal attainment. Assessments occur at baseline, post-intervention, and at 4- and 12-week follow-up.
As a pilot randomised controlled trial, this study will generate the first controlled evidence on adjunctive cortical neuromodulation alongside tSCS-based rehabilitation, while also producing feasibility data to inform the design of a future definitive multicentre trial.
Detailed description
Background: Cervical spinal cord injury (SCI) results in severe upper limb impairment, with restoration of hand and arm function ranked as the highest rehabilitation priority by individuals with tetraplegia. Transcutaneous spinal cord stimulation (tSCS) has emerged as a promising approach for enhancing upper limb recovery. Intermittent theta burst stimulation (iTBS), an efficient form of repetitive transcranial magnetic stimulation, can enhance cortical excitability and descending motor drive. However, the benefit of combining these complementary neuromodulation modalities to simultaneously target supraspinal and spinal circuits has not been evaluated in a controlled trial.
Objective: This study aims to evaluate the feasibility, safety, and preliminary efficacy of combined cortical neuromodulation (iTBS) and spinal neuromodulation (tSCS) versus tSCS alone, each paired with standardized upper limb rehabilitation, for improving upper limb motor function in chronic incomplete cervical SCI.
Methods: This single-center, two-arm, assessor-blinded, pilot randomized controlled trial will enroll 24 adults aged 21 to 65 years with chronic (more than 12 months post-injury) incomplete cervical SCI (American Spinal Injury Association Impairment Scale grade C or D, neurological level C2 to C8). Participants will be randomized 1:1 to receive either iTBS combined with tSCS plus standardized upper limb rehabilitation or tSCS plus upper limb rehabilitation alone. Interventions will be delivered twice weekly for 12 weeks (24 sessions). The primary outcome is the change in Upper Extremity Motor Score from baseline to 12 weeks. Secondary outcomes include measures of upper limb function, independence, spasticity, corticospinal excitability, quality of life, and goal attainment. Assessments will be conducted at baseline, post-intervention, and at 4-week and 12-week follow-up.
Conclusions: This pilot trial will provide the first controlled evidence on whether adjunctive cortical neuromodulation via iTBS produces additional upper limb motor recovery beyond tSCS-based rehabilitation in chronic incomplete cervical SCI. Feasibility data and effect size estimates will inform the design of a subsequent multicenter confirmatory trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Single-center, two-arm, assessor-blinded, pilot randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| iTBS combined with tSCS plus standardized upper limb rehabilitation | Experimental | Device: Transcranial Magnetic Stimulation, Device: Transcutaneous Spinal Cord StimulationInterventions are delivered twice weekly for 12 weeks (24 sessions): iTBS over M1 followed by combined tSCS plus upper limb rehabilitation (45-60 min). tSCS uses a constant-current stimulator with 5×10 cm electrodes at C3-C4 and/or C6-C7, with reference electrodes over the ASIS or clavicles. Parameters: biphasic pulses at 30 Hz, 1 ms pulses with 10 kHz carrier frequency, intensity 40-120 mA, delivered continuously for ~45 minutes. iTBS is delivered over the M1 hand area contralateral to the more impaired limb. Protocol: 600 pulses (3-pulse bursts at 50 Hz, repeated at 5 Hz, 80% AMT over 3-4 minutes. Upper limb rehabilitation follows immediately, supervised by a physiotherapist and occupational therapist, based on the Up-LIFT trial protocol. Sessions include reaching, finger movements, pinch, grip, bimanual coordination, and individualised functional tasks, with difficulty progressed systematically. |
| tSCS plus standardized upper limb rehabilitation only | Active comparator | Device: Transcutaneous Spinal Cord StimulationInterventions are delivered twice weekly for 12 weeks (24 sessions). tSCS uses a constant-current stimulator with 5×10 cm electrodes at C3-C4 and/or C6-C7, with reference electrodes over the ASIS or clavicles. Parameters: biphasic pulses at 30 Hz, 1 ms pulses with 10 kHz carrier frequency, intensity 40-120 mA, delivered continuously for ~45 minutes. The carrier frequency reduces skin discomfort and enables deeper dorsal root activation. Upper limb rehabilitation follows immediately, supervised by a physiotherapist and occupational therapist, based on the Up-LIFT trial protocol. Sessions include reaching, finger movements, pinch, grip, bimanual coordination, and individualised functional tasks, with difficulty progressed systematically. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Chronicity: More than 12 months post-injury at enrollment
- Injury type: Traumatic or non-traumatic incomplete cervical SCI, neurological level C2 to C8
- AIS classification: Grade C or D
- UEMS: 10 to 20 out of 25 on the more impaired side; lower bound 10 ensures sufficient voluntary activation for task training and elicitable MEPs, upper bound avoids ceiling effects.
- Grip strength: MMT grade 3 or higher in finger flexors (C8 myotome) on at least one side.
Key exclusion criteria (10 listed)
- Seizure history: History of seizures or epilepsy
- Implanted devices: Intracranial metallic implants, cochlear implants, cardiac pacemakers, or other implanted electronic devices. Cervical spinal instrumentation (e.g., posterior rods, plates, or screws at C2 to T1) is not an exclusion for tSCS provided overlying skin is intact; participants with hardware directly beneath planned electrode sites will undergo low-intensity test stimulation during screening, and electrode placement will be shifted by one interspace if current distortion, focal discomfort, or unexpected motor thresholds are observed. Intracranial hardware remains an absolute exclusion for iTBS.
- Prior craniotomy: Prior neurosurgical procedure involving craniotomy
- Pregnancy: Currently pregnant or intending to become pregnant during the study period
- Psychiatric or cognitive: Active psychiatric illness (eg, untreated major depression, psychosis) or cognitive impairment precluding informed consent
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 |
|---|---|---|
| Transcranial Magnetic StimulationRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that enhances cortical excitability and corticospinal drive. Intermittent theta burst stimulation (iTBS), a brief patterned form of rTMS, produces lasting facilitatory effects and is more time-efficient. Evidence indicates rTMS improves motor function, reduces spasticity, and enhances neuroplasticity in SCI. | Device | iTBS combined with tSCS plus standardized upper limb rehabilitation |
| Transcutaneous Spinal Cord StimulationTranscutaneous spinal cord stimulation (tSCS) is a non-invasive neuromodulation technique that delivers electrical stimulation over the spine to activate sensory afferents and enhance spinal motor circuit excitability. Early studies showed it can enable voluntary movement even in motor-complete spinal cord injury (SCI), with subsequent research demonstrating improvements in motor function, standing, and walking in incomplete SCI. Evidence suggests tSCS modulates both spinal and corticospinal pathways, supporting neuroplasticity. The Up-LIFT trial (2024) provided strong clinical evidence, showing that tSCS combined with rehabilitation significantly improved upper limb strength and function in chronic cervical SCI, with 72% of participants meeting effectiveness endpoints and no serious adverse events. Later studies confirmed its safety in home and community settings, though standardization and larger trials remain needed. | Device | iTBS combined with tSCS plus standardized upper limb rehabilitation, tSCS plus standardized upper limb rehabilitation only |
Primary outcome
Upper Extremity Motor Score (UEMS)
Time frame: Week 0
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Upper Extremity Motor Score (UEMS)
Time frame: Week 12
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Upper Extremity Motor Score (UEMS)
Time frame: Week 16
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Upper Extremity Motor Score (UEMS)
Time frame: Week 24
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
44 secondary outcomes
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
Time frame: Week 0
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
Time frame: Week 12
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
Time frame: Week 16
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)
Time frame: Week 24
Grip/Pinch Strength
Time frame: Week 0
Grip/Pinch Strength
Time frame: Week 12
Grip/Pinch Strength
Time frame: Week 16
Grip/Pinch Strength
Time frame: Week 24
Nine-Hole Peg Test
Time frame: Week 0
Nine-Hole Peg Test
Time frame: Week 12
Nine-Hole Peg Test
Time frame: Week 16
Nine-Hole Peg Test
Time frame: Week 24
Box and Block Test
Time frame: Week 0
Box and Block Test
Time frame: Week 12
Box and Block Test
Time frame: Week 16
Box and Block Test
Time frame: Week 24
Capabilities of Upper Extremity Test (CUE-T)
Time frame: Week 0
Capabilities of Upper Extremity Test (CUE-T)
Time frame: Week 12
Capabilities of Upper Extremity Test (CUE-T)
Time frame: Week 16
Capabilities of Upper Extremity Test (CUE-T)
Time frame: Week 24
Spinal Cord Independence Measure III (SCIM-III)
Time frame: Week 0
Spinal Cord Independence Measure III (SCIM-III)
Time frame: Week 12
Spinal Cord Independence Measure III (SCIM-III)
Time frame: Week 16
Spinal Cord Independence Measure III (SCIM-III)
Time frame: Week 24
R2-R1 in Modified Tardieu Scale
Time frame: Week 0
R2-R1 in Modified Tardieu Scale
Time frame: Week 6
R2-R1 in Modified Tardieu Scale
Time frame: Week 12
R2-R1 in Modified Tardieu Scale
Time frame: Week 16
R2-R1 in Modified Tardieu Scale
Time frame: Week 24
Central Motor Conduction Time (CMCT)
Time frame: Week 0
Central Motor Conduction Time (CMCT)
Time frame: Week 12
Central Motor Conduction Time (CMCT)
Time frame: Week 16
Central Motor Conduction Time (CMCT)
Time frame: Week 24
peak-to-peak amplitude of motor evoked potential (MEP)
Time frame: Week 0
peak-to-peak amplitude of motor evoked potential (MEP)
Time frame: Week 12
peak-to-peak amplitude of motor evoked potential (MEP)
Time frame: Week 16
peak-to-peak amplitude of motor evoked potential (MEP)
Time frame: Week 24
EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
Time frame: Week 0
EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
Time frame: Week 12
EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L)
Time frame: Week 24
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 14 May 2026.
- Derived from this study: PubMed 42292339Shankar R, Tang N, Chandran G. Combined repetitive transcranial magnetic stimulation and transcutaneous spinal cord stimulation for upper limb recovery in chronic incomplete cervical spinal cord injury: protocol for a pilot randomized controlled trial. Front Neurosci. 2026 May 28;20:1833493. doi: 10.3389/fnins.2026.1833493. eCollection 2026.
- Individual participant dataSharing planned: No. According to institution research polices, research agreement needs to be signed before sharing individual data with external parties.
Related trials for Spinal Cord Injuries (SCI)
Enrolling by invitation
Brief Prolonged Exposure Therapy Versus Clinical Standard to Reduce Posttraumatic Stress Post Spinal Cord Injury
Spinal Cord Injuries, PTSD
RecruitingPhase 2/3
Pilot Study of Galantamine to Treat Metabolic Syndrome in People With Chronic Traumatic Spinal Cord Injury (SCI)
Spinal Cord Injury, Traumatic Spinal Cord Injury
Active, not recruitingObservational study
SCIVAX: Biomarkers of Immune Dysfunction and Vaccine Responsiveness in Chronic SCI
Spinal Cord Injuries, Traumatic Spinal Cord Injury
Enrolling by invitation
Long-Term Clinical, Health Economic, and Process Evaluation of Intensive Technology-Integrated Motor Rehabilitation in Chronic Neurological Conditions (INTeRAcT-bis)
Stroke, Spinal Cord Injuries (SCI)
Recruiting
At-Home Genital Nerve Stimulation for SCI Bowel
Spinal Cord Injury
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.
Tang Ning, PhD contact
Gobinathan Chandran, MBBS principal investigator
NUH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation and Transcutaneous Spinal Cord Stimulation in people with Spinal Cord Injuries (SCI), run by National University Hospital, Singapore at 1 site in Singapore.
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 11 inclusion and 10 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 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Contact Gobinathan Chandran, MBBS (+65 94575924, gobinathan_chandran@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Upper Extremity Motor Score (UEMS) (time frame: Week 0). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07586644, which also lists 1 linked publication.
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 14 May 2026.