StrokeStimNeuroNCT05766059
Novel Non-invasive Brain Stimulation Techniques in Neurological Rehabilitation
A study testing Transcranial Magnetic Stimulation in people with Stroke and Hemiparesis, run by Istituto Auxologico Italiano at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke, Hemiparesis, Phantom Limb Pain
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteItaly
- Study dates
- 8 Feb 2023to 30 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Istituto Auxologico Italiano IRCCS
Milan, Lombardy, 20122
Nadia Bolognini, PhD, +390261911 ext. 6127, n.bolognini@auxologico.it
About this study
Official title: 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.
Read the 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).
- Conditions
- Stroke, Hemiparesis, Phantom Limb Pain
- Being tested
- Transcranial Magnetic Stimulation
- Keywords
- Transcranial Magnetic Stimulation, Paired Associative Stimulation, Stroke, Motor cortex, Phantom limb pain
- Medical subject headings
- Stroke, Paresis, Phantom Limb
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Also called TMS, Paired associative stimulation
The standard PAS protocol will be compared with the mirrorPAS protocol.
| Study group | Role | What they receive |
|---|---|---|
| [Phase 1] Stroke patients with upper-limb hemiparesis | Experimental | Not described Receives: Device: Transcranial Magnetic Stimulation |
| [Phase 2] Patients with phantom limb pain (PLP) | Experimental | Not described Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in motor-evoked potentials (MEP)
[Phase 1, only in stroke patients] peak-to-peak MEP amplitude
Measured: At baseline and after the administration of the PAS protocols
Change in functional mapping of phantom limb cortical areas
[Phase 2, only in PLP patients]
Measured: At baseline and after the administration of the PAS protocols
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study start8 Feb 2023
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Istituto Auxologico ItalianoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Auxologico Italiano
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nadia Bolognini, PhD, Principal investigator, Laboratorio di Neuropsicologia, IRCCS Istituto Auxologico Italiano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05766059
- Sponsor's protocol ID
- 25C212
- Acronym
- StimNeuro
- Status last verified
- Sep 2025
- First submitted
- 28 Feb 2023
- Last updated
- 17 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34302877Guidali 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.
PubMed 32289688Kaur 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.
PubMed 30583983Castel-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.
PubMed 19060132Stefan 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.
PubMed 10686179Hummel 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.
PubMed 16857577Bolognini 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.
PubMed 27080070Rossi 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.
PubMed 33243615
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05766059
- Acronym / sponsor ID
- StimNeuro / 25C212
- Conditions
- Stroke, Hemiparesis, Phantom Limb Pain
- Keywords
- Transcranial Magnetic Stimulation, Paired Associative Stimulation, Stroke, Motor cortex, Phantom limb pain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Istituto Auxologico ItalianoUniversity, hospital or other
- Study start
- 8 Feb 2023 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 13 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| [Phase 1] Stroke patients with upper-limb hemiparesis | Experimental | Device: Transcranial Magnetic Stimulation |
| [Phase 2] Patients with phantom limb pain (PLP) | Experimental | Device: Transcranial Magnetic Stimulation |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic StimulationAlso: TMS, Paired associative stimulationThe standard PAS protocol will be compared with the mirrorPAS protocol. | Device | [Phase 1] Stroke patients with upper-limb hemiparesis, [Phase 2] Patients with phantom limb pain (PLP) |
Primary outcome
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
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]
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Background: PubMed 34302877Guidali 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.
- Background: PubMed 32289688Guidali 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.
- Background: PubMed 30583983Kaur 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.
- Background: PubMed 19060132Castel-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.
- Background: PubMed 10686179Stefan 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.
- Background: PubMed 16857577Hummel 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.
- Background: PubMed 27080070Bolognini 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.
- Background: PubMed 33243615Rossi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nadia Bolognini, PhD principal investigator
Laboratorio di Neuropsicologia, IRCCS Istituto Auxologico Italiano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Stroke and Hemiparesis, run by Istituto Auxologico Italiano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nadia Bolognini, PhD (+390261911 ext. 6127, n.bolognini@auxologico.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in motor-evoked potentials (MEP) (time frame: At baseline and after the administration of the PAS protocols). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05766059, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2025.