Novel Non-invasive Brain Stimulation Techniques in Neurological Rehabilitation

NCT ID: NCT05766059

Last Updated: 2025-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-08

Study Completion Date

2026-09-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Stroke Hemiparesis Phantom Limb Pain

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

In a first phase \[Phase 1\], the study aims to assess the motor and neurophysiological effects of a cross-modal 'mirror-PAS' protocol in stroke patients with upper-limb hemiparesis, compared to the standard excitatory M1-PAS.

In a second phase of the study \[Phase 2\], we will test the efficacy of the aforementioned cross-modal PAS in a population of amputated patients affected by phantom limb pain (PLP).
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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[Phase 1] Stroke patients with upper-limb hemiparesis

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type DEVICE

The standard PAS protocol will be compared with the mirrorPAS protocol.

[Phase 2] Patients with phantom limb pain (PLP)

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type DEVICE

The standard PAS protocol will be compared with the mirrorPAS protocol.

Interventions

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Transcranial Magnetic Stimulation

The standard PAS protocol will be compared with the mirrorPAS protocol.

Intervention Type DEVICE

Other Intervention Names

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TMS Paired associative stimulation

Eligibility Criteria

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Inclusion Criteria

* 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


* 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

* 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)


* contraindications to TMS (Rossi et all, 2021)
* other neurological, orthopedical or psychiatric conditions
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Istituto Auxologico Italiano

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nadia Bolognini, PhD

Role: PRINCIPAL_INVESTIGATOR

Laboratorio di Neuropsicologia, IRCCS Istituto Auxologico Italiano

Locations

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Istituto Auxologico Italiano IRCCS

Milan, Lombardy, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Nadia Bolognini, PhD

Role: CONTACT

+390261911 ext. 6127

Facility Contacts

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Nadia Bolognini, PhD

Role: primary

+390261911 ext. 6127

References

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Guidali G, Roncoroni C, Bolognini N. Paired associative stimulations: Novel tools for interacting with sensory and motor cortical plasticity. Behav Brain Res. 2021 Sep 24;414:113484. doi: 10.1016/j.bbr.2021.113484. Epub 2021 Jul 21.

Reference Type BACKGROUND
PMID: 34302877 (View on PubMed)

Guidali G, Carneiro MIS, Bolognini N. Paired Associative Stimulation drives the emergence of motor resonance. Brain Stimul. 2020 May-Jun;13(3):627-636. doi: 10.1016/j.brs.2020.01.017. Epub 2020 Feb 5.

Reference Type BACKGROUND
PMID: 32289688 (View on PubMed)

Kaur A, Guan Y. Phantom limb pain: A literature review. Chin J Traumatol. 2018 Dec;21(6):366-368. doi: 10.1016/j.cjtee.2018.04.006. Epub 2018 Dec 4.

Reference Type BACKGROUND
PMID: 30583983 (View on PubMed)

Castel-Lacanal E, Marque P, Tardy J, de Boissezon X, Guiraud V, Chollet F, Loubinoux I, Moreau MS. Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients. Neurorehabil Neural Repair. 2009 May;23(4):366-72. doi: 10.1177/1545968308322841. Epub 2008 Dec 5.

Reference Type BACKGROUND
PMID: 19060132 (View on PubMed)

Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain. 2000 Mar;123 Pt 3:572-84. doi: 10.1093/brain/123.3.572.

Reference Type BACKGROUND
PMID: 10686179 (View on PubMed)

Hummel FC, Cohen LG. Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke? Lancet Neurol. 2006 Aug;5(8):708-12. doi: 10.1016/S1474-4422(06)70525-7.

Reference Type BACKGROUND
PMID: 16857577 (View on PubMed)

Bolognini N, Russo C, Edwards DJ. The sensory side of post-stroke motor rehabilitation. Restor Neurol Neurosci. 2016 Apr 11;34(4):571-86. doi: 10.3233/RNN-150606.

Reference Type BACKGROUND
PMID: 27080070 (View on PubMed)

Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

Reference Type BACKGROUND
PMID: 33243615 (View on PubMed)

Other Identifiers

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25C212

Identifier Type: -

Identifier Source: org_study_id

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