Clinical trial NCT06999876: The Effect of Combined Transcranial Pulse Current Stimulation (tPCS) and Transcutaneous Electrical Nerve Stimulation (TENS) on Lower Limb Motor Function in Subacute to Chronic Stroke Patients With Hemiplegia (COMPENSATOR-Stroke)
Official title: The Effect of Combined Transcranial Pulse Current Stimulation (tPCS) and Transcutaneous Electrical Nerve Stimulation (TENS) on Lower Limb Motor Function in Subacute to Chronic Stroke Patients With Hemiplegia: A Double-blind, Sham-controlled, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke Patients With Hemiplegia or Hemiparesis in the Subacute Stage
Keywords: Transcranial Pulsed Current Simulation
Transcutaneous Electrical Nerve Stimulation
Lower limb motor function recovery
Spasticity
Gait dysfunction
Standing balance
Ambulation
Stroke
Hemiplegia
Hemiparesis
Lead sponsor: National University Health System, Singapore
Sponsor class: OTHER
First posted: 2025-05-31
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Active tPCS + TENS treatment (Intervention arm) This group will receive active TENS treatment delivered through Channel 2, 3 and 4 of The AscenZ-VIII Stimulator via 6\*9cm Silica gel electrodes on top of the tPCS that is delivered through Channel 1. The placement of the electrodes will be on the part of the spinal segment innervating the lower limbs (L1-L5), the adductor muscles and the gastrocnemius muscles.

Sham tPCS + TENS treatment (Control arm) Sham tPCS current will be delivered through Channel 1, while active TENS treatment delivered through Channel 2, 3 and 4 of The AscenZ-VIII Stimulator via surface electrodes. The placement of electrodes will be exactly the same as the active tPCS montage.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to evaluate the effects of high frequency tPCS + TENS compared to Sham device stimulation + TENS (Control) in lower limb motor function recovery in stroke patients with hemiplegia or hemiparesis in the subacute stage.The main questions it aims to answer are:

Primary objective - To evaluate the effects of high frequency tPCS + TENS compared to Sham device stimulation + TENS (Control) in lower limb motor function recovery, in stroke patients with hemiplegia or hemiparesis in the subacute stage

Secondary Objectives -

1. To evaluate the effects of high frequency tPCS + TENS in treatment of lower limb spasticity related to stroke.
2. To evaluate the effects of high frequency tPCS + TENS in gait function improvement post stroke, including walking speed, mobility, balance and walking endurance.
3. To evaluate the effects of high frequency tPCS on pain, mood and QOL.

Researchers will compare the effects of high frequency tPCS + TENS to a control group which involves intervention with Sham device stimulation + TENS.

Participants will:

* Be identified, recruited and have baseline assessments during screening period
* First undergo a mandatory 2-hour device training at Visit 2 to ensure device competence.
* Proceed with up to 7 days of habituation for device use and tolerability.
* Carry out daily intervention sessions of 30 minutes for 30 days at home or inpatient setting.
* Phone call follow-up (Telephone/ Video Call Interview) 2 weeks post intervention
* Clinic visit at day 30 post intervention with allowance of + 7 days for study assessments
* Clinic visit at day 90 post intervention with allowance of +/- 7 days for study assessments
* Update study coordinators via messaging platforms with regards to device issues, adverse events, any other reporting or questions

Detailed description: In this prospective, double-blind, sham-controlled randomized control study, a total of 90 participants with hemiplegia or hemiparesis post stroke will be recruited from National University Hospital (NUH) and Alexandra Hospital (AH) inpatient wards and outpatient clinic. 45 participants will be randomized to the intervention arm (Intervened with tPCS + TENS) and 45 participants will be randomized to the control arm (Sham device stimulation + TENS).

The study will consist of a Screening period of up to 14 days. Participants who fulfil all the inclusion criteria will be consented and recruited during this screening period, constituting as Visit 1 (Recruitment). During this visit, PI/ Co-I obtaining consent will ensure that patient/ caregiver meets the following criteria:

1. For patients where the caregiver is administering the treatment, study team will ensure that they are the primary caregiver of the patient.
2. Patient/ caregiver must be comfortable and committed in following directions for device usage.
3. Patient/ caregiver must not have mental disability.

After confirmation of the above criteria, patient/ caregiver will undergo a 2-hour hands-on training at NUH by trained study team.

A set of training slides titled "AscenZ-VIII User training slides" that is adapted from the standard "Instruction Manual AscenZVIII" will be utilized for the training session for patient/ caregiver. After which, a checklist titled "Home Training Checklist" will be completed by both the trainer and patient/caregiver. This checklist is aimed to ensure that all necessary components of training have been covered by the trainer and also for trainers to indicate confidence of patient/ caregiver during the training before both trainer and patient/ caregiver signs as a form of training acknowledgement.

Post training, a copy of the standard "Instruction Manual AscenZVIII" will be given to patient/ caregiver. Study team will emphasize to patient/ caregiver that they can contact study team at any juncture where they need additional clarifications relating to the device.

Depending on the hospitalization status at time of screening, the patient will be seen in the inpatient ward or specialist outpatient clinic at day 14 which is considered as Visit 2 (Randomization with allowance + 3 days). Allowance of up to 3 days is given in the event day 14 falls on a weekend/long weekend. Following Visit 2 (Randomization with allowance + 3 days), up to 3 days of habituation for device use and tolerability will take place. Participants will be required to receive the intervention at low levels of intensity to allow conditioning for the habituation period. Because of the nature of the intervention, it may cause some discomfort to the participants, hence conditioning will increase the tolerability of the treatment for the participants.

Intervention with tPCS will take place over 30 days either in the inpatient setting of NUH and AH or in the home setting, while the rehabilitation therapy sessions with physiotherapy and occupational therapy happening concurrently as per existing clinical treatment protocol. Treatment with tPCS and TENS will consist of a daily session of 30 minutes for 30 days. Compliance will be checked by research assistant via telephone or video call interview at regular interval. One group will be randomised to the sham device stimulation + TENS (Control) arm and one group will be randomised to the active device intervention arm (intervened with tPCS + TENS). The sham device stimulation (Control) arm have electrode placement in the exact manner as the treatment arm but receive very little transcranial stimulation such that the output is negligible.

Assessment will be done at the time of recruitment which constitutes as Visit 1 (Recruitment), and again at the Visit 3 (Last day of intervention, Day 30 post intervention with allowance of + 7 days) and Visit 4 (Final follow-up, Day 90 post intervention with allowance of + 7 days).

Activities and assessments that are done under research activities include:

Visit 1 (Recruitment)

* Eligibility screening
* Consent taking
* Blood Pressure (Research procedure if not done clinically)
* Standard physio and occupational therapy sessions as prescribed by patient's physician (Research procedure if not done clinically)
* Stroke deficit scale (Baseline mRS, NIHSS)
* Clinical measures on lower limb motor function (Lower Extremity - Fugl Meyer Assessment Baseline, Time UP and Go Baseline, 6 Minute Walk Test Baseline, 10 Meter Walk Test Baseline)
* Clinical measures on lower limb spasticity - Hip, Knee Flexion, Ankle Flexor, Plantar (Modified Ashworth Scale Baseline, Modified Tardieu Scale Baseline)
* Balance (Berg Balance Scale Baseline)
* Pain (Pain Numeric Rating Scale Baseline)
* Mood (Hospital Anxiety and Depression Scale Baseline)
* FIM
* EQ5D-5L Baseline
* Overall length of stay in hospital
* Outcomes events/Complications

Visit 2 (Randomization with allowance of + 3 days):

* Randomization
* Commence first day of habituation, up to 3 days

Follow-up Telephone/ Video Call Interview, at 2 weeks post intervention (Research procedure)

- Patients will be asked regarding: i) Device related side-effects ii) Hospital re-admissions iii) Changes in medications iv) Device management (eg. Difficulties faced while using the device, Device working condition Damage to device, Device parts that require replacement, Re-supply of consumables, etc)

Visit 3 (Last day of intervention, Day 30 post intervention with allowance of + 7 days):

* Treatment group OR Control Group - 30min daily for 30 days
* Stroke deficit scale (mRS, NIHSS)
* Clinical measures on lover limb motor function (Lower Extremity - Fugl Meyer Assessment, Time Up and Go, 6 Minute Walk Test, 10 Meter Walk Test )
* Clinical measures on lower limb spasticity - Hip, Knee Flexion, Ankle Flexor, Plantar (Modified Ashworth Scale, Modified Tardieu Scale)
* Balance (Berg Balance Scale)
* Pain (Pain Numeric Rating Scale)
* Mood (Hospital Anxiety and Depression Scale)
* FIM
* EQ5D-5L
* Overall length of stay in hospital
* Outcomes events/Complications

Visit 4 (Final follow-up, Day 90 post intervention with allowance of +/- 7 days):

* Stroke deficit scale (mRS, NIHSS)
* Clinical measures on lower limb motor function (Lower Extremity - Fugl Meyer Assessment, Time Up and Go, 6 Minute Walk Test, 10 Meter Walk Test)
* Clinical measures on lower limb spasticity - Hip, Knee Flexion, Ankle Flexor, Plantar (Modified Ashworth Scale, Modified Tardieu Scale)
* Balance (Berg Balance Scale)
* Pain (Pain Numeric Rating Scale)
* Mood (Hospital Anxiety and Depression Scale)
* FIM
* EQ5D-5L
* Overall length of stay in hospital
* Outcomes events/Complications

Management of adverse events (AEs and SAEs):

At recruitment (Visit 1), patients/ caregivers will be informed to take note and save research coordinator's contact number stated in the ICF. Patients/ caregivers will be reminded to contact research coordinators if patients experience any AE/SAE stated on ICF section 6 from the day of recruitment up to randomization (Visit 2). At randomization (Visit 2) it will again be emphasized to patients and caregivers that they are to continue to monitor for AE/SAE. During the duration of habituation through to the 30-day intervention period, patients/ caregivers are additionally required to report to the study coordinators with regards to any discomfort or issues with the device before proceeding with intervention. During the habituation and the 30-day intervention period, study coordinator will be keeping close contact with the patient/ caregiver by means of messaging apps to ensure compliance to the treatment regime and for AE/SAE reporting.

Patients who are starting the intervention in the inpatient setting will be monitored by the study team for any adverse events.

Eligibility criteria: Inclusion Criteria:

1. Participants aged 21 years old and below 80 years old with a clinically diagnosed first onset ischaemic stroke confirmed by imaging modalities such as computerised tomography (CT) or magnetic resonance imaging (MRI). Previous transient ischemic attack or clinically silent infarct detected by CT/MRI are not considered as previous stroke.
2. Participants within the subacute stage of stroke (Within 14 days from stoke onset)
3. Able to walk with or without assistance
4. Able to understand instructions and give informed consent

Exclusion Criteria:

1. History of craniotomy or placement of implant materials/ device in the body that may affect NIBS including, but not limited to, deep brain stimulator, cardiac implant, cochlear implant
2. Intracranial haemorrhage in the cortical regions
3. History of epilepsy or seizures
4. History of major depression and a history of psychotic disorders
5. Contraindications to tPCS/TENS e.g., pregnancy, presence of skin lesion at the intended treatment areas.
6. Concurrent use of benzodiazepine pyschoactive class of drugs which may affect effects of tPCS
7. Concurrent use of anti-seizure medications (ASMs) which may affect effects of tPCS
8. Presence of significant cognitive impairment/ aphasia rendering patient unable to comply with the treatment protocol
9. Presence of disabling comorbidities that compromises limb function such as orthopaedics or neurological pathologies other than stroke
10. Previous treatments of the lower limb spasticity with botulinum toxin, or alcohol.
11. Prior history of non-invasive brain stimulations

Primary outcomes:
measure: Lower Extremity Portion of Fugl-Meyer Assessment (LE-FMA)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: Functional Independence Measure (FIM)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
Secondary outcomes:
measure: Modified Ashworth Scale (MAS)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: Modified Tardieu Scale (MTS)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: Time Up and Go (TUG)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: 10-meter Walk Test (10MWT)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: 6-minute Walk Test
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: Berg Balance Scale (BBS)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: Pain Numeric Rating Scale (NRS)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: EQ5D-5L
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: From enrollment to Day 90 post intervention (with allowance of + 7 days).
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Alexandra Hospital
Study officials:
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