Transcranial Magnetic Stimulation and Mental Representation Techniques for the Treatment of Stroke Patients

NCT ID: NCT04815486

Last Updated: 2023-11-30

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

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-01

Study Completion Date

2023-05-31

Brief Summary

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An immersive multimodal BCI-VR training and bilateral rTMS protocols are likely to complement their effects achieving a stronger neuroplasticity enhancement in stroke patients. Both have been used separately for the treatment of motor sequelae in the upper limbs after stroke. The main objective of this study is to carry out a double-blind, randomized, controlled trial aiming to study the clinical effect of Neurow system (NeuroRehabLab, Lisbon, Portugal) over bilateral rTMS plus conventional rehabilitation in upper limb motor sequelae after subacute stroke (3 to 12 months). We will look for changes in 1. Isometric strength in upper limb, 2. Functional motor scales of upper limb, 3. Hand dexterity 4. Cortical excitability changes. The investigators in the present project hypothesize that both neuromodulation techniques combined will be superior to the use of rTMS alone as adjuvant therapy to conventional rehabilitation.

Detailed Description

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Stroke is a leading cause of long-term disability, it reduces mobility in more than half of stroke survivors age 65 and over.

Despite the lack of objective prognostic factors regarding the patient´s functionality after a stroke, we know that age, the level of initial disability, and the location and size of the lesion are elements that affect the evolution of post-stroke rehabilitation.

After stroke, the recovery of lost functions in the brain is achieved thanks to reorganizing networks in a process known as plasticity. Some damaged brain tissue may recover, or undamaged areas take over some functions.

One of the most relevant aspects of the rehabilitation prognosis is the time of evolution. After stroke, improvement is noticeably reduced over the second month, finding stabilization around the sixth month. One of the reasons for this is the reduction of neuroplasticity. There are indicative studies that reflect that, six months after a stroke, more than 60% of subjects will have a non-functional hand for Basic Activities of Daily Living (BADL), and 20-25% will not be able to walk without assistance. This determines the important global burden that stroke represents. It is relevant to emphasize the degree of disability after the rehabilitation process will be determined by the combination of existing motor, sensory and neuropsychological deficiencies.

In the last years, several non-invasive neuromodulation techniques have been shown efficient to enhance plasticity and stroke recovery. Among these interventions we can find exogenous neuromodulation, meaning that the neuromodulator stimulus comes from an external source, as is the case with rTMS (repetitive transcranial magnetic stimulation) which has the capacity to change the cortical excitability depending on the frequency of the magnetic pulses. Low frequencies (≤ 1 Hz) reduce local neural activity and high frequencies (≥ 5 Hz) increase cortical excitability. This technique has been successfully used bilaterally, stimulating the injured hemisphere and inhibiting the healthy one, to treat the interhemispheric inhibition phenomenon in stroke patients as it influences stroke recovery.

On the other hand, there are endogenous neuromodulation techniques that depend on the capacity of the subject to modulate its own brain activity. This can be achieved using neurofeedback (NFB), this consists of recording information of brain activity using electroencephalography (EEG) or functional magnetic resonance (fMRI) and displaying it to the subject in such way that he can receive a real time information of his own brain function. Virtual reality allows a new dimension on the neurofeedback immersion, and is likely to increase its efficacy. Stroke patients have been trained to reinforce certain EEG rhythms related with motor performance using NFB technique showing favourable effects on rehabilitation outcomes.

Some other techniques aiming to increase brain plasticity use the practice of imagination of movement of the affected hemibody. This is known as motor imagery and can be also enhanced through the use of brain computer interfaces. All the neuromodulation techniques are used to complement but not as a replacement of conventional rehabilitation.

On one hand exogenous neuromodulation effects are produced mainly by changes directly induced in cortical excitability and on the other hand endogenous neuromodulation is believed to have more widespread subcortical effects. One of the probable causes of the short-term effects of these techniques is the ceiling effect of changes in cortical excitability that can be achieved non-invasively, but despite of the good results achieved with the use of non-invasive neuromodulation techniques individually, there is a shortage of validated neurorehabilitation protocols that integrate different approaches that have been proven to be effective individually.

Neurow system (NeuroRehabLab, Lisbon, Portugal) is an immersive multimodal BCI-VR training system that combines motor imagery and neurofeedback through BCIs, using virtual reality has been designed to be used in chronic stroke patients, its efficacy has been shown in a pilot study.

Both approaches, the Neurow system (NeuroRehabLab, Lisbon, Portugal) and bilateral rTMS protocols are likely to complement their effects achieving a stronger neuroplasticity enhancement in stroke patients. Both have been used separately for the treatment of motor sequelae in the upper limbs after stroke. The effects of these combined techniques are not likely to be based only in the increase of cortical excitability but also on subcortical mechanisms.

The main objective of this study is to carry out a double-blind, randomized, controlled trial aiming to study the clinical effect of Neurow system (NeuroRehabLab, Lisbon, Portugal) over bilateral rTMS plus conventional rehabilitation in upper limb motor sequelae after subacute stroke (3 to 12 months). We will look for changes in 1. Isometric strength in upper limb, 2. Functional motor scales of upper limb, 3. Hand dexterity 4. Cortical excitability changes. Our main hypothesis is that both neuromodulation techniques combined will be superior to the use of rTMS alone as adjuvant therapy to conventional rehabilitation.

This protocol combines techniques that have proven to be cost-effective. If it is shown that the clinical improvement with this combination is significant, it will be open a new line of combined neuromodulation approaches to reach and effective method for the upper limb motor neurorehabilitation of after a stroke.

Conditions

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Stroke

Keywords

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Stroke rTMS Motor Imagery BCI

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

The clinical trial will follow an AB/BA crossover design with a counterbalanced assignment, in which the first 50% of the sample will be assigned to order AB and the second 50% to order BA. The washout period between therapies A and B will be always a month.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bilateral rTMS combined with MI through a BCI training platform in VR with NeuRow

Sequential active rTMS at low frequency (healthy hemisphere) and high-frequency (injured hemisphere) application during 10 sessions in two weeks, and Motor Imagery (MI) treatment through the BCI training paradigm in VR (NeuRow) for 12 sessions in four weeks (3 sessions a week).The first 6 MI-neurofeedback sessions will carry out after bilateral stimulation with rTMS (i.e., rTMS as a priming method during the first two weeks), and the last 6 sessions, without rTMS as prior priming during the last two weeks

Group Type EXPERIMENTAL

Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type DEVICE

Active rTMS in 10 daily sessions in two weeks of sequential application of: 90% RMT at 1Hz, 1000 pulses/day, 25s inter train on M1 of lesioned hemisphere and 90% RMT at 10Hz, 1000 pulses/day, 50s inter train on M1 of healthy hemisphere.

Repetitive TMS in bilateral cortical primary motor area

Sequential active rTMS at low frequency (healthy hemisphere) and high-frequency (injured hemisphere) application during 10 sessions in two weeks.

Group Type ACTIVE_COMPARATOR

Motor Imagery (MI) through a Brain-Computer Interface (BCI) training platform in Virtual Reality (VR) with NeuRow

Intervention Type DEVICE

It will consist of a combination of the bilateral rTMS protocol and the MI-neurofeedback training. During this therapy, the patient received 10 consecutive daily sessions of bilateral rTMS (Monday to Friday, two weeks), with the same stimulation parameters as another therapy, and 12 non-consecutive sessions of MI-neurofeedback (three times a week for four weeks). The first 6 MI-neurofeedback sessions were carried out after bilateral stimulation with rTMS (i.e., rTMS as a priming method during the first two weeks), and the last 6 sessions, without rTMS as prior priming during the last two weeks.

Interventions

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Repetitive Transcranial Magnetic Stimulation (rTMS)

Active rTMS in 10 daily sessions in two weeks of sequential application of: 90% RMT at 1Hz, 1000 pulses/day, 25s inter train on M1 of lesioned hemisphere and 90% RMT at 10Hz, 1000 pulses/day, 50s inter train on M1 of healthy hemisphere.

Intervention Type DEVICE

Motor Imagery (MI) through a Brain-Computer Interface (BCI) training platform in Virtual Reality (VR) with NeuRow

It will consist of a combination of the bilateral rTMS protocol and the MI-neurofeedback training. During this therapy, the patient received 10 consecutive daily sessions of bilateral rTMS (Monday to Friday, two weeks), with the same stimulation parameters as another therapy, and 12 non-consecutive sessions of MI-neurofeedback (three times a week for four weeks). The first 6 MI-neurofeedback sessions were carried out after bilateral stimulation with rTMS (i.e., rTMS as a priming method during the first two weeks), and the last 6 sessions, without rTMS as prior priming during the last two weeks.

Intervention Type DEVICE

Other Intervention Names

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Therapy A Therapy B

Eligibility Criteria

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Inclusion Criteria

Older than 18 years old.

Ischemic or hemorrhagic cerebrovascular injury diagnosed by a neurologist and who have at least one brain-imaging test.

The onset of hemispheric ischemic or hemorrhagic stroke\> 3 months.

Presence of upper limb motor sequelae due to stroke.

Sufficient cognitive ability to understand and perform tasks: Token Test\> 11.

Stability in antispastic medication for more than 5 days.

Able to read and write.

Exclusion Criteria

History of seizure or brain

Pacemakers, medication pumps, metal implants in the head (except dental implants)

Clinical unstability

Other pre-existing neurological diseases or previous cerebrovascular accidents with sequelae.

Sensory aphasia

Previous TMS after stroke

Hemispatial neglect,

Flaccid paralysis Brunnstrom's stage \< 1

Visual problems
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Beata María Ana

OTHER

Sponsor Role collaborator

Universidad Francisco de Vitoria

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Juan Pablo Romero Muñoz, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Francisco de Vitoria, Facultad de Ciencias Experimentales

Locations

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Hospital Beata Maria Ana

Madrid, , Spain

Site Status

Countries

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Spain

References

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Vourvopoulos A, Bermudez I Badia S. Motor priming in virtual reality can augment motor-imagery training efficacy in restorative brain-computer interaction: a within-subject analysis. J Neuroeng Rehabil. 2016 Aug 9;13(1):69. doi: 10.1186/s12984-016-0173-2.

Reference Type BACKGROUND
PMID: 27503007 (View on PubMed)

Vourvopoulos A, Jorge C, Abreu R, Figueiredo P, Fernandes JC, Bermudez I Badia S. Efficacy and Brain Imaging Correlates of an Immersive Motor Imagery BCI-Driven VR System for Upper Limb Motor Rehabilitation: A Clinical Case Report. Front Hum Neurosci. 2019 Jul 11;13:244. doi: 10.3389/fnhum.2019.00244. eCollection 2019.

Reference Type BACKGROUND
PMID: 31354460 (View on PubMed)

Takeuchi N, Izumi S. Maladaptive plasticity for motor recovery after stroke: mechanisms and approaches. Neural Plast. 2012;2012:359728. doi: 10.1155/2012/359728. Epub 2012 Jun 26.

Reference Type BACKGROUND
PMID: 22792492 (View on PubMed)

Takeuchi N, Tada T, Toshima M, Matsuo Y, Ikoma K. Repetitive transcranial magnetic stimulation over bilateral hemispheres enhances motor function and training effect of paretic hand in patients after stroke. J Rehabil Med. 2009 Nov;41(13):1049-54. doi: 10.2340/16501977-0454.

Reference Type BACKGROUND
PMID: 19894000 (View on PubMed)

Zhang L, Xing G, Shuai S, Guo Z, Chen H, McClure MA, Chen X, Mu Q. Low-Frequency Repetitive Transcranial Magnetic Stimulation for Stroke-Induced Upper Limb Motor Deficit: A Meta-Analysis. Neural Plast. 2017;2017:2758097. doi: 10.1155/2017/2758097. Epub 2017 Dec 21.

Reference Type BACKGROUND
PMID: 29435371 (View on PubMed)

Pichiorri F, Morone G, Petti M, Toppi J, Pisotta I, Molinari M, Paolucci S, Inghilleri M, Astolfi L, Cincotti F, Mattia D. Brain-computer interface boosts motor imagery practice during stroke recovery. Ann Neurol. 2015 May;77(5):851-65. doi: 10.1002/ana.24390. Epub 2015 Mar 27.

Reference Type BACKGROUND
PMID: 25712802 (View on PubMed)

Dionisio A, Duarte IC, Patricio M, Castelo-Branco M. The Use of Repetitive Transcranial Magnetic Stimulation for Stroke Rehabilitation: A Systematic Review. J Stroke Cerebrovasc Dis. 2018 Jan;27(1):1-31. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.008. Epub 2017 Oct 27.

Reference Type BACKGROUND
PMID: 29111342 (View on PubMed)

Sasaki N, Mizutani S, Kakuda W, Abo M. Comparison of the effects of high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke. J Stroke Cerebrovasc Dis. 2013 May;22(4):413-8. doi: 10.1016/j.jstrokecerebrovasdis.2011.10.004. Epub 2011 Dec 15.

Reference Type BACKGROUND
PMID: 22177936 (View on PubMed)

Pfurtscheller G, Neuper C, Muller GR, Obermaier B, Krausz G, Schlogl A, Scherer R, Graimann B, Keinrath C, Skliris D, Wortz M, Supp G, Schrank C. Graz-BCI: state of the art and clinical applications. IEEE Trans Neural Syst Rehabil Eng. 2003 Jun;11(2):177-80. doi: 10.1109/TNSRE.2003.814454.

Reference Type BACKGROUND
PMID: 12899267 (View on PubMed)

Cogne M, Gil-Jardine C, Joseph PA, Guehl D, Glize B. Seizure induced by repetitive transcranial magnetic stimulation for central pain: Adapted guidelines for post-stroke patients. Brain Stimul. 2017 Jul-Aug;10(4):862-864. doi: 10.1016/j.brs.2017.03.010. Epub 2017 Mar 23. No abstract available.

Reference Type BACKGROUND
PMID: 28359831 (View on PubMed)

Duncan PW, Wallace D, Lai SM, Johnson D, Embretson S, Laster LJ. The stroke impact scale version 2.0. Evaluation of reliability, validity, and sensitivity to change. Stroke. 1999 Oct;30(10):2131-40. doi: 10.1161/01.str.30.10.2131.

Reference Type BACKGROUND
PMID: 10512918 (View on PubMed)

Other Identifiers

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Handboost

Identifier Type: -

Identifier Source: org_study_id