Novel Non-invasive Brain Stimulation Techniques in Neurological Rehabilitation (StimNeuro)

September 11, 2025 updated by: Istituto Auxologico Italiano

Novel Non-invasive Brain Stimulation Techniques in Neurological Rehabilitation: Cross-modal Paired Associative Stimulation (PAS) Protocols to Promote Plastic Reorganization in Stroke and Phantom Limb Pain Patients

Paired associative stimulation (PAS) is a non-invasive brain stimulation protocol, where two stimuli (a peripheral and a cortical one, the latter delivered with transcranial magnetic stimulation - TMS) are repeatedly associated to enhance plasticity in the brain. In the present study, a new cross-modal, visuo-motor PAS protocol - called "mirror-PAS"- will be tested as a possible non-invasive brain stimulation treatment in neurological rehabilitation to promote motor recovery and pain reduction.

Participants will perform the standard PAS targeting the motor system and the recently developed mirror-PAS in two separate sessions. The investigators will compare the possible effect of the protocols in terms of neurophysiological and behavioral outcomes to identify the optimal PAS method to enhance plasticity and promote sensory-motor function.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The motor recovery of the upper limb function, particularly of the hand, is challenging in neurological rehabilitation. Transcranial magnetic stimulation (TMS) is a form of non-invasive brain stimulation that can enhance motor recovery, though promoting brain plasticity of the brain.

In this study, researchers will use a TMS protocol called Paired Associative Stimulation (PAS), in which two stimuli (e.g., a cortical stimulus - delivered with TMS - and a peripheral stimulus) are repeatedly associated to promote associative plasticity in the primary motor cortex (M1).

The objective is to explore the clinical efficacy of a newly developed cross-modal PAS protocol -the so-called "mirror-PAS"- as a possible motor rehabilitation treatment in patients with upper limb motor disorders, investigating its neurophysiological and behavioural effects. The innovative aspect of mirror-PAS is to act on a more extended visuomotor network, featured by the functional properties of the mirror neuron system (MNS). Indeed, in the mirror-PAS, a visual stimulus depicting a hand movement is repeatedly paired with a TMS pulse over M1. In the healthy, this protocol was found effective in modulating neurophysiological responses of the motor cortex (i..e, MEPs), hence inducing these effects bypassing the afferent somatosensory pathway exploited by the standard PAS protocols. This may represent a clinical advantage allowing the promotion of motor recovery through the induction of a plastic reorganization in the damaged motor system by gaining access through a potentially spared MNS.

The project's first phase aims to assess the motor and neurophysiological effects of mirror-PAS in stroke patients with upper-limb hemiparesis, compared to the standard excitatory M1-PAS (whose effects are well known in the literature, even if still debated).

In the second phase, we will test the efficacy of the mirror-PAS in a population of amputated patients affected by phantom limb pain (PLP).

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Lombardy
      • Milan, Lombardy, Italy, 20122
        • Recruiting
        • Istituto Auxologico Italiano IRCCS
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria for stroke patients:

  • age from 18 to 85 years
  • single, unilateral, hemispheric stroke (cortical or sub-cortical areas)
  • stroke confirmed by neuroimaging (CT or MRI)
  • stroke at least 4 months before enrollment
  • hemiparesis of the upper limb resulting from stroke or hemianesthesia clinically documented

Exclusion criteria for stroke patients:

  • contraindications to TMS (Rossi et all, 2021)
  • other neurological conditions (e.g., Parkinson's Disease, Multiple Sclerosis, ALS)
  • other orthopedic condition that affected the hand (e.g., carpal tunnel syndrome)

Inclusion criteria for PLP patients:

  • age from 18 to 90 years
  • amputation of one part of the upper limb at least 2 months before enrollment
  • presence of stable phantom limb pain at least 2 months prior to enrollment

Exclusion criteria for PLP patients:

  • contraindications to TMS (Rossi et all, 2021)
  • other neurological, orthopedical or psychiatric conditions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: [Phase 1] Stroke patients with upper-limb hemiparesis
Device: Transcranial Magnetic Stimulation
The standard PAS protocol will be compared with the mirrorPAS protocol.
Other Names:
  • TMS
  • Paired associative stimulation
Experimental: [Phase 2] Patients with phantom limb pain (PLP)
Device: Transcranial Magnetic Stimulation
The standard PAS protocol will be compared with the mirrorPAS protocol.
Other Names:
  • TMS
  • Paired associative stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in motor-evoked potentials (MEP)
Time Frame: At baseline and after the administration of the PAS protocols
[Phase 1, only in stroke patients] peak-to-peak MEP amplitude
At baseline and after the administration of the PAS protocols
Change in functional mapping of phantom limb cortical areas
Time Frame: At baseline and after the administration of the PAS protocols
[Phase 2, only in PLP patients]
At baseline and after the administration of the PAS protocols

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Auxologico Italiano

Investigators

  • Principal Investigator: Nadia Bolognini, PhD, Laboratorio di Neuropsicologia, IRCCS Istituto Auxologico Italiano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 8, 2023

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

February 28, 2023

First Submitted That Met QC Criteria

March 10, 2023

First Posted (Actual)

March 13, 2023

Study Record Updates

Last Update Posted (Estimated)

September 17, 2025

Last Update Submitted That Met QC Criteria

September 11, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25C212

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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