Paired Associative Stimulation (PAS) for Stroke Rehabilitation (PAS-Stroke)

Comparison of Two Deep TMS Protocols With Paired Associative Stimulation (PAS) for the Treatment of Motor Impairement in Stroke Patients

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke Ischemic
• Intervention / Treatment: Device: A multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel); Device: A multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel)

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Beersheba, Israel
    • Soroke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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); 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).; Device: A 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.
Sham Comparator: Sham PAS protocol; 40% of individual UH RMT	Device: A 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).; Device: A 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to one year after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to one year after enrollement
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.	From enrollement to one year after enrollment
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.	From enrollement to one year after enrollement
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.	From enrollement to one year after enrollment
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.	From enrollement to one year after enrollment
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.	From enrollment to one year after enrollment
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.	From enrollement to one year after enrollment
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.	From enrollment to one year after enrollment
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.	From enrollment to one year after enrollment

Collaborators and Investigators

• Sponsor: Soroka University Medical Center
• Collaborators: Ben-Gurion University of the Negev

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2019
• Primary Completion (Actual): April 15, 2026
• Study Completion (Estimated): October 28, 2026

Study Registration Dates

• First Submitted: September 11, 2025
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Rehabilitation; Stroke; Hemiparesis; Upper-extremity; Paired Associative Stimulaton
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Ischemic Stroke; Stroke; Paresis
• Other Study ID Numbers: 0270-19-SOR; MOH_2018-06-07_002349 (Registry Identifier: Israeli Ministry of Health Research Ethics Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No