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Active, not recruitingNCT07691099PAS-StrokeUpdated Jul 8, 2026

Paired Associative Stimulation (PAS) for Stroke Rehabilitation

An interventional study of A multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel) and A multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel) in Stroke Ischemic, sponsored by Soroka University Medical Center. Active, not recruiting at 1 site in Israel. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-07-08.

Sponsored by Soroka University Medical Center · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study summary

Paired associative stimulation (PAS) delivered with multi-channel deep transcranial magnetic stimulation (dTMS) may enhance motor recovery in patients with first-ever ischemic stroke. This study evaluates whether dTMS-PAS targeting both primary motor cortices (M1-M1) improves upper-extremity hemiparesis when administered at the early subacute stage (up to three weeks poststroke).

Read the detailed description

Unilateral ischemic stroke disrupts the activity balance between the hemispheres, which hinder brains' recovery and treatments' efficiency. The most common and pervasive acquired postischemic stroke functional disorder is hemiparesis of the upper-extremity. The limited impact of conventional rehabilitation therapies is attributed to their inability to restore the interhemispheric balance. Thus, PAS protocol, delivered using dTMS, may benefit patients by regaining the interhemispheric balance. PAS is delivered over two different cortical brain areas, and the modulation of interhemispheric balance is determined by which area is stimulated by the first pulse and which by the second. In this study, the investigators apply a dTMS-PAS protocol over the two primary motor cortices, to restore the activity balance between M1-M1, alleviate upper-extremity hemiparesis symptoms, and promote functional recovery.

02

Conditions studied

  • Stroke Ischemic

Keywords

  • Stroke
  • Upper-extremity
  • Hemiparesis
  • Paired Associative Stimulaton
  • Rehabilitation
03

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • The diagnosis of stroke is based on computed tomography (CT) or magnetic resonance imaging (MRI).
  • The diagnosis of first acute ischemic stroke in unilateral hemisphere within 3 weeks after onset.
  • Clinically evident arm hemiparesis attributable to acute ischemic stroke.
  • Age of 18-85 years.
  • The ability to sign a informed consent.

Exclusion criteria

Exclusion Criteria:

  • Any previous stroke.
  • Minor stroke with non-disabling deficit or rapidly improving neurological symptoms.
  • Prior participation in the present study, or planned participation in another therapeutic trial, prior to the final assessment in this trial.
  • Current participation in another study with an investigational drug or device.
  • Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
  • Any intracranial surgery, intraspinal surgery, or serious head trauma (any head injury that required hospitalization) within the past 3 months prior to participation in the current study.
  • Presence or history of intracranial neoplasm (except small meningiomas) or arteriovenous malformation.
  • Intracranial aneurysm, unless surgically or endovascularlytreated more than 3 months prior to participation in the current study.
  • Seizure at the onset of stroke or a history of epilepsy.
  • Life expectancy less than 3 months.
  • Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease.
  • Other serious illness, e.g., severe hepatic, cardiac, or renal failure.
  • Acute myocardial infarction or complex disease that may confound treatment assessment.
  • Cognitive or verbal impairment that prevented understanding of or cooperation with the research study.

Under the following medical conditions, treatment was stopped, and patients were excluded from the study:

  • Acute worsening of > 4 points on the NIH stroke scale (NIHSS).
  • Acute symptoms of headache nausea and vomiting suggestive of possible sICH.
  • Occurrence of seizures.
  • Appearance of a new ventricular arrhythmia, tachycardia, fibrillation etc. or a new life-threatening supraventricular arrhythmia (e.g., rapid atrial fibrillation or supraventricular tachycardia).
  • Symptomatic bradycardia - heart rate less than 50 beats per min.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Active PAS protocol

    120% of individual unaffected-hemisphere (UH) resting motor threshold (RMT)

    Device: A multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel)

  • Sham comparator
    Sham PAS protocol

    40% of individual UH RMT

    Device: A multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel)

Interventions

  • DeviceA multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel)

    Active dTMS-PAS stimulation is applied at 120% of the individual RMT of the UH. Each session consists of 600 paired pulses, delivered bilaterally over M1-M1, with an inter-pulse interval (IPI) of 10 miliseconds (ms) and an inter-stimulus interval (ISI) of 3 seconds (s), for a total duration of 30 minutes (m).

  • DeviceA multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel)

    Sham PAS is delivered using the same coil, applied at 40% of the individual RMT of the UH. Each session consists of identical number of paired pulses and timing parameters as in the Active PAS arm, but at an intensity insufficient to induce cortical modulation.

05

What researchers measure

Primary outcomes

  1. Fugl - Meyer Assessment for Upper Extremity (FMA-UE) Score

    The FMA-UE is a standardized, clinical, stroke-specific performance scale assessing motor impairement of the upper-extremity. It includes 33 items across four domains (shoulder-arm, wrist, hand, coordination), each scored 0-2 (total range 0-66). Higher scores indicate better motor function. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.

    Time frame: From enrollment to one year after enrollment

Secondary outcomes

  1. Action Research Arm Test (ARAT) Score

    The ARAT is a standardized clinical measure of arm-hand functional capacity consisting of 19 items across grasp, pinch, and gross movement (score range 0-57). Higher scores indicate better function. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.

    Time frame: From enrollment to one year after enrollement

  2. Jebsen-Taylor Hand Function Test (JTHFT) Time

    The JTHFT is a standardized clinical 7-task timed assessment of functional hand performance (writing, page turning, object lifting, etc.). Each task is scored by the time required to complete it, with a maximum allowed time of 120 seconds per task. Lower total time indicates better function. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.

    Time frame: From enrollement to one year after enrollment

  3. Box and Blocks Test (BBT) Score

    The BBT is a standardized clinical measure, assessing unilateral manual dexterity by counting the number of blocks transferred in 60 seconds. Higher values indicate greater dexterity. Normative reference values are available by age, sex, and hand dominance, allowing interpretation relative to typical performance. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.

    Time frame: From enrollement to one year after enrollement

  4. Hand-Held Dynamometry Grip Strength

    Grip strengh is assessed using a standardized clinical hand-held dynamometer, which provides an objective numerical measure of upper-extremity muscle strength. Higher values indicate greater strength. Normative reference values are available by age, sex, and hand dominance, allowing interpretation relative to typical performance. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.

    Time frame: From enrollement to one year after enrollment

  5. Disabilities of the ARM, Shoulder, and Hand (DASH) Score

    The DASH is a 30-item self-report questionnaire assessing upper-extremity disability (0-100%). Higher scores indicate greater disability. Assessment Schedule: Pre-treatment, Post-treatment, 2 and 12 months.

    Time frame: From enrollement to one year after enrollment

  6. Resting Motor Threshold (RMT) via transcranial magnetic stimulation (TMS)

    RMT is the minimum TMS intensity required to elicit a measurable electromyography (EMG) response in the abductor pollicis brevis. Lower thresholds indicate higher corticospinal excitability. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.; plus pre- and post-protocol measurements during the first two PAS sessions.

    Time frame: From enrollment to one year after enrollment

  7. Motor evoked potential (MEP) Amplitude

    MEP amplitude (peak-to-peak EMG response) reflects corticospinal excitability following TMS. Higher amplitudes indicate greater excitability. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.; plus pre- and post-protocol measurements during the first two PAS sessions.

    Time frame: From enrollement to one year after enrollment

  8. MEP Latency

    Latency is the time from TMS pulse to the initial MEP peak, reflecting conduction speed. Shorter latency indicated faster neural conduction. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.; plus pre- and post-protocol measurements during the first two PAS sessions.

    Time frame: From enrollment to one year after enrollment

  9. Interhemispheric inhibition (IHI) via PAS

    IHI quantifies inhibitory influence from one motor cortex to the other using PAS. Greater inhibition reflects stronger interhemispheric suppression. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke; plus pre- and post-protocol measurements during the first two PAS sessions.

    Time frame: From enrollment to one year after enrollment

06

Study locations

1 site
  • Soroke University Medical Center
    Beersheba, Israel
07

References and documents

Individual participant data

Plan to share: Yes

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07691099
Lead sponsor
Soroka University Medical Center
Collaborators
Ben-Gurion University of the Negev
Responsible party
Iuly Treger MD (Director of Rehabilitation Department, Soroka University Medical Center) — Principal investigator
First posted
Jul 8, 2026
Start date
Nov 10, 2019
Primary completion
Apr 15, 2026
Completion
Oct 28, 2026 (estimated)
Last update
Jul 8, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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