Novel Non-invasive Brain Stimulation Techniques in Neurological Rehabilitation

NCT05766059 | Recruiting

• 1 other identifier: 25C212
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Stroke; Hemiparesis; Phantom Limb Pain

Keywords

Transcranial Magnetic Stimulation; Paired Associative Stimulation; Stroke; Motor cortex; Phantom limb pain

Outcome Measures

Primary Outcomes (2)

• Change from baseline in motor-evoked potentials (MEP)

  \[Phase 1, only in stroke patients\] peak-to-peak MEP amplitude

  At baseline and after the administration of the PAS protocols

• Change in functional mapping of phantom limb cortical areas

  \[Phase 2, only in PLP patients\]

  At baseline and after the administration of the PAS protocols

Study Arms (2)

[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

Interventions

Transcranial Magnetic Stimulation DEVICE

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

Also known as: TMS, Paired associative stimulation

[Phase 1] Stroke patients with upper-limb hemiparesis; [Phase 2] Patients with phantom limb pain (PLP)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead

Study Sites (1)

Istituto Auxologico Italiano IRCCS

Milan, Lombardy, 20122, Italy

RECRUITING

Related Publications (8)

• 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.

  PMID: 34302877 BACKGROUND

• 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.

  PMID: 32289688 BACKGROUND

• 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.

  PMID: 30583983 BACKGROUND

• 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.

  PMID: 19060132 BACKGROUND

• 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.

  PMID: 10686179 BACKGROUND

• 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.

  PMID: 16857577 BACKGROUND

• 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.

  PMID: 27080070 BACKGROUND

• 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.

  PMID: 33243615 BACKGROUND

MeSH Terms

Conditions

Stroke; Paresis; Phantom Limb

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Nadia Bolognini, PhD

  Laboratorio di Neuropsicologia, IRCCS Istituto Auxologico Italiano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadia Bolognini, PhD

CONTACT

+390261911; n.bolognini@auxologico.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 13, 2023
• Study Start: February 8, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: September 17, 2025

Record last verified: 2025-09

Locations

IT (1)