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

NCT04815486 | Completed

• 1 other identifier: Handboost
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke

Keywords

Stroke; rTMS; Motor Imagery; BCI

Outcome Measures

Primary Outcomes (16)

• Change in Dynamometry

  A handheld analogic dynamometer (Jamar® Plus+ Hand Dynamometer, 0-90 kg) will be used to assess isometric grip strength. Patients will be positioned in a straight back chair with both feet on the floor and the forearm resting on a stable surface. Each patient will be instructed to assume a position of adducted and neutrally rotated shoulder. For the arm to be tested, the elbow was flexed to 90º, the forearm and wrist will be in neutral positions, and the fingers will be flexed as needed for a maximal contraction. Patients will perform a maximal isometric grip contraction until they reach maximal force output. Three measures will be taken with 1-minute rest between test, and the mean value will be recorded

  Baseline

• Change in Dynamometry

  A handheld analogic dynamometer (Jamar® Plus+ Hand Dynamometer, 0-90 kg) will be used to assess isometric grip strength. Patients will be positioned in a straight back chair with both feet on the floor and the forearm resting on a stable surface. Each patient will be instructed to assume a position of adducted and neutrally rotated shoulder. For the arm to be tested, the elbow was flexed to 90º, the forearm and wrist will be in neutral positions, and the fingers will be flexed as needed for a maximal contraction. Patients will perform a maximal isometric grip contraction until they reach maximal force output. Three measures will be taken with 1-minute rest between test, and the mean value will be recorded

  From Baseline at 2 weeks

• Change in Dynamometry

  A handheld analogic dynamometer (Jamar® Plus+ Hand Dynamometer, 0-90 kg) will be used to assess isometric grip strength. Patients will be positioned in a straight back chair with both feet on the floor and the forearm resting on a stable surface. Each patient will be instructed to assume a position of adducted and neutrally rotated shoulder. For the arm to be tested, the elbow was flexed to 90º, the forearm and wrist will be in neutral positions, and the fingers will be flexed as needed for a maximal contraction. Patients will perform a maximal isometric grip contraction until they reach maximal force output. Three measures will be taken with 1-minute rest between test, and the mean value will be recorded

  From Baseline at 4 weeks

• Change in Dynamometry

  A handheld analogic dynamometer (Jamar® Plus+ Hand Dynamometer, 0-90 kg) will be used to assess isometric grip strength. Patients will be positioned in a straight back chair with both feet on the floor and the forearm resting on a stable surface. Each patient will be instructed to assume a position of adducted and neutrally rotated shoulder. For the arm to be tested, the elbow was flexed to 90º, the forearm and wrist will be in neutral positions, and the fingers will be flexed as needed for a maximal contraction. Patients will perform a maximal isometric grip contraction until they reach maximal force output. Three measures will be taken with 1-minute rest between test, and the mean value will be recorded

  From Baseline at 6 weeks

• Change in Fugl-Meyer Assessment for upper extremity score

  It is an observational rating scale that assesses sensorimotor impairments in post-stroke patients. It also includes four subscales: A. Upper Extremity (0-36), B. Wrist (0-10), C. Hand (0-14), D. Coordination/Speed (0-6) composing a total maximum score of 66 points. The therapist will rate each item according to direct observation of the motor performance, using a 3-point ordinal scale (0 = cannot perform, 1 = performs partially, and 2 = performs fully) with lower scores indicating more impairments. The FMA is easy to use and has excellent validity, reliability, and responsiveness.

  Baseline

• Change in Fugl-Meyer Assessment for upper extremity score

  It is an observational rating scale that assesses sensorimotor impairments in post-stroke patients. It also includes four subscales: A. Upper Extremity (0-36), B. Wrist (0-10), C. Hand (0-14), D. Coordination/Speed (0-6) composing a total maximum score of 66 points. The therapist will rate each item according to direct observation of the motor performance, using a 3-point ordinal scale (0 = cannot perform, 1 = performs partially, and 2 = performs fully) with lower scores indicating more impairments. The FMA is easy to use and has excellent validity, reliability, and responsiveness.

  From Baseline at 2 weeks

• Change in Fugl-Meyer Assessment for upper extremity score

  It is an observational rating scale that assesses sensorimotor impairments in post-stroke patients. It also includes four subscales: A. Upper Extremity (0-36), B. Wrist (0-10), C. Hand (0-14), D. Coordination/Speed (0-6) composing a total maximum score of 66 points. The therapist will rate each item according to direct observation of the motor performance, using a 3-point ordinal scale (0 = cannot perform, 1 = performs partially, and 2 = performs fully) with lower scores indicating more impairments. The FMA is easy to use and has excellent validity, reliability, and responsiveness.

  From Baseline at 4 weeks

• Change in Fugl-Meyer Assessment for upper extremity score

  It is an observational rating scale that assesses sensorimotor impairments in post-stroke patients. It also includes four subscales: A. Upper Extremity (0-36), B. Wrist (0-10), C. Hand (0-14), D. Coordination/Speed (0-6) composing a total maximum score of 66 points. The therapist will rate each item according to direct observation of the motor performance, using a 3-point ordinal scale (0 = cannot perform, 1 = performs partially, and 2 = performs fully) with lower scores indicating more impairments. The FMA is easy to use and has excellent validity, reliability, and responsiveness.

  From Baseline at 6 weeks

• Change in Stroke Impact Scale score

  It is a stroke-specific quality of life instrument to assess the consequences of stroke and to determine the quality of life improvement after stroke rehabilitation. It presents 4 subscales, but only hand function domain will be evaluated. Lower scores indicate more impairment in quality of life. The Minimal Detectable Change (MDC) and Clinically Important Difference (CID) of the hand function subscale are 25.9 and 17.8 points, respectively.

  Baseline

• Change in Stroke Impact Scale score

  It is a stroke-specific quality of life instrument to assess the consequences of stroke and to determine the quality of life improvement after stroke rehabilitation. It presents 4 subscales, but only hand function domain will be evaluated. Lower scores indicate more impairment in quality of life. The Minimal Detectable Change (MDC) and Clinically Important Difference (CID) of the hand function subscale are 25.9 and 17.8 points, respectively.

  From Baseline at 2 weeks

• Change in Stroke Impact Scale score

  It is a stroke-specific quality of life instrument to assess the consequences of stroke and to determine the quality of life improvement after stroke rehabilitation. It presents 4 subscales, but only hand function domain will be evaluated. Lower scores indicate more impairment in quality of life. The Minimal Detectable Change (MDC) and Clinically Important Difference (CID) of the hand function subscale are 25.9 and 17.8 points, respectively.

  From Baseline at 4 weeks

• Change in Stroke Impact Scale score

  It is a stroke-specific quality of life instrument to assess the consequences of stroke and to determine the quality of life improvement after stroke rehabilitation. It presents 4 subscales, but only hand function domain will be evaluated. Lower scores indicate more impairment in quality of life. The Minimal Detectable Change (MDC) and Clinically Important Difference (CID) of the hand function subscale are 25.9 and 17.8 points, respectively.

  From Baseline at 6 weeks

• Change in Motricity Index of the Arm

  The upper limb section of the MI assesses muscle strength in 3 muscle groups, including grip, elbow flexion, and shoulder separation. Each movement is scored discreetly (0 if there is no movement, 9 if the movement is palpable, 14 if the movement is visible, 19 if the movement is against gravity, 25 if the movement is against resistance and 33 if the movement is normal ), obtaining a total score for the upper limb that ranges from 0 (severely affected) to 100 (normal). This assessment methodology has been widely used in rehabilitation progress evaluation and counts with a normalized and weighted scoring system.

  Baseline

• Change in Motricity Index of the Arm

  The upper limb section of the MI assesses muscle strength in 3 muscle groups, including grip, elbow flexion, and shoulder separation. Each movement is scored discreetly (0 if there is no movement, 9 if the movement is palpable, 14 if the movement is visible, 19 if the movement is against gravity, 25 if the movement is against resistance and 33 if the movement is normal ), obtaining a total score for the upper limb that ranges from 0 (severely affected) to 100 (normal). This assessment methodology has been widely used in rehabilitation progress evaluation and counts with a normalized and weighted scoring system.

  From Baseline at 2 weeks

• Change in Motricity Index of the Arm

  The upper limb section of the MI assesses muscle strength in 3 muscle groups, including grip, elbow flexion, and shoulder separation. Each movement is scored discreetly (0 if there is no movement, 9 if the movement is palpable, 14 if the movement is visible, 19 if the movement is against gravity, 25 if the movement is against resistance and 33 if the movement is normal ), obtaining a total score for the upper limb that ranges from 0 (severely affected) to 100 (normal). This assessment methodology has been widely used in rehabilitation progress evaluation and counts with a normalized and weighted scoring system.

  From Baseline at 4 weeks

• Change in Motricity Index of the Arm

  The upper limb section of the MI assesses muscle strength in 3 muscle groups, including grip, elbow flexion, and shoulder separation. Each movement is scored discreetly (0 if there is no movement, 9 if the movement is palpable, 14 if the movement is visible, 19 if the movement is against gravity, 25 if the movement is against resistance and 33 if the movement is normal ), obtaining a total score for the upper limb that ranges from 0 (severely affected) to 100 (normal). This assessment methodology has been widely used in rehabilitation progress evaluation and counts with a normalized and weighted scoring system.

  From Baseline at 6 weeks

Secondary Outcomes (23)

• Change in Electroencephalogram data

  Baseline

• Change in Electroencephalogram data

  At 2 weeks from Baseline

• Change in Electroencephalogram data

  At 4 weeks from Baseline

• Change in Electroencephalogram data

  At 6 weeks from Baseline

• Change in Nottingham Sensory Assessment (NSA)

  Baseline

Study Arms (2)

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

EXPERIMENTAL

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

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Repetitive TMS in bilateral cortical primary motor area

ACTIVE COMPARATOR

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

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

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) 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.

Also known as: Therapy A

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

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

Also known as: Therapy B

Repetitive TMS in bilateral cortical primary motor area

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidad Francisco de Vitoria: lead
• Hospital Beata María Ana: collaborator

Study Sites (1)

Hospital Beata Maria Ana

Madrid, 28007, Spain

Location

Related Publications (11)

• 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.

  PMID: 27503007 BACKGROUND

• 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.

  PMID: 31354460 BACKGROUND

• 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.

  PMID: 22792492 BACKGROUND

• 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.

  PMID: 19894000 BACKGROUND

• 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.

  PMID: 29435371 BACKGROUND

• 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.

  PMID: 25712802 BACKGROUND

• 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.

  PMID: 29111342 BACKGROUND

• 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.

  PMID: 22177936 BACKGROUND

• 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.

  PMID: 12899267 BACKGROUND

• 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.

  PMID: 28359831 BACKGROUND

• 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.

  PMID: 10512918 BACKGROUND

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Magnetic Stimulation; PUVA Therapy

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Ultraviolet Therapy; Phototherapy

Study Officials

• Juan Pablo Romero Muñoz, MD PhD

  Universidad Francisco de Vitoria, Facultad de Ciencias Experimentales

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 25, 2021
• Study Start: May 1, 2021
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: November 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Six months at the end of the study.
• Access Criteria: Individual anonymized participant data will be available to other researchers under request.

Locations

ES (1)