Investigating the Effects of Transcranial Stimulation to Advance Stroke Rehabilitation

NCT06842095 | Recruiting

• 1 other identifier: PID17878
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Non-invasive brain stimulation (NIBS) has the potential to boost rehabilitation after stroke by creating a 'pro-plastic' environment, where the brain is more adaptable in response to movement (motor) training. However, responses to classical NIBS protocols are highly variable. Movement-related changes in specific brain rhythms have previously been shown to be related to recovery of hand/arm function after a stroke. The investigators propose to use NIBS to target movement-related activity in the beta band (13-30Hz) within the motor cortical regions of the brain. The investigators will use a type of NIBS called transcranial alternating current stimulation (tACS), which uses a sinusoidally-varying electrical current where the stimulation frequency is determined to be relevant to the underlying brain rhythms of interest, and the stimulation timed to coincide with specific phases of the hand/arm movement. The primary aim is to investigate whether beta-tACS improves upper limb movement in stroke survivors.

Conditions

Stroke; Upper Limb Function

Keywords

Non-Invasive Brain Stimulation; Stroke; Upper Limb; Electroencephalography; Transcranial Alternating Current Stimulation; Beta Oscillations

Outcome Measures

Primary Outcomes (1)

• Reaching Performance

  Performance on the reaching task, assessed using a motion sensor as the error (deviation from the ideal path) in cubic centimeters. Higher numbers indicate worse error/reaching performance.

  From the first stimulation session to the completion of the third and final session, an average of 1 month

Secondary Outcomes (2)

• Movement-related Brain Rhythms

  From the first stimulation session to the completion of the third and final session, an average of 1 month

• Hand Function

  From the first stimulation session to the completion of the third and final session, an average of 1 month

Other Outcomes (11)

• Smoothness of reaching movement (peaks)

  From the first stimulation session to the completion of the third and final session, an average of 1 month

• Smoothness of reaching movement (arrest periods)

  From the first stimulation session to the completion of the third and final session, an average of 1 month

• Smoothness of reaching movement (Jerk)

  From the first stimulation session to the completion of the third and final session, an average of 1 month

Study Arms (2)

Active Stimulation (beta-tACS)

EXPERIMENTAL

Participants will receive one session of active stimulation (beta-tACS) to the ipsilesional hemisphere. The electrode montage will include one electrode positioned on the scalp over the left or right motor cortex (either C3 or C4 using the international 10-20 EEG system), depending on the location of the stroke, and a second electrode over posterior area (Pz). A low intensity of stimulation (max. 4 mA peak to peak amplitude) will be used for up to 30 minutes in total (delivered in short bouts of up to 5 seconds based on the timing of movement of the upper limb).

Other: Transcranial Alternating Current Stimulation (beta-tACS)

Sham Stimulation (tACS)

SHAM COMPARATOR

Participants will receive one session of sham stimulation. The electrode placement will be the same as for the experimental condition, but duration or timing of stimulation will be insufficient to induce intended brain rhythm changes.

Other: Transcranial Alternating Current Stimulation (sham)

Interventions

Transcranial Alternating Current Stimulation (beta-tACS) OTHER

The study intervention is transcranial alternating current stimulation (tACS). The electrode montage will include one electrode positioned on the scalp over the left or right motor cortex (either C3 or C4 using the international 10-20 EEG system), depending on the location of the stroke, and a second electrode over posterior area (Pz). A low intensity of stimulation (max. 4 mA peak to peak amplitude) will be used for up to 30 minutes in total (delivered in short bouts of up to 5 seconds based on the timing of movement of the upper limb).

Also known as: Non Invasive Brain Stimulation, beta tACS

Active Stimulation (beta-tACS)

Transcranial Alternating Current Stimulation (sham) OTHER

The comparator is sham stimulation. Stimulation is delivered for a very short duration or timed in such a way relative to movement to mimic the scalp sensations of the active stimulation without delivering stimulation that would be anticipated to impact relevant brain activity rhythms.

Also known as: tACS (sham)

Sham Stimulation (tACS)

Eligibility Criteria

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

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• Aged 18 years or above.
• Clinical diagnosis of stroke affecting the upper limb, with sufficient ability to perform the upper limb reaching task.
• At least 3 months post-stroke and discharged from inpatient care.

You may not qualify if:

• Inability to follow task instructions.
• Other neurological condition affecting movement (e.g. Parkinson's Disease, Multiple Sclerosis).
• Standard contraindications to non-invasive brain stimulation (TMS, tACS). including (but not limited to) the presence of intracranial metallic or magnetic hardware, seizures, pregnancy, and the presence of a pacemaker or other stimulators/implants.
• Insufficient verbal and written English to comprehend the study and provide informed consent.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Oxford Centre for Functional MRI of the Brain (FMRIB)

Oxford, OX3 9DU, United Kingdom

RECRUITING

Related Publications (29)

• Wischnewski M, Schutter DJLG, Nitsche MA. Effects of beta-tACS on corticospinal excitability: A meta-analysis. Brain Stimul. 2019 Nov-Dec;12(6):1381-1389. doi: 10.1016/j.brs.2019.07.023. Epub 2019 Jul 28.

  PMID: 31405789 BACKGROUND

• Toledo DR, Manzano GM, Barela JA, Kohn AF. Cortical correlates of response time slowing in older adults: ERP and ERD/ERS analyses during passive ankle movement. Clin Neurophysiol. 2016 Jan;127(1):655-663. doi: 10.1016/j.clinph.2015.05.003. Epub 2015 May 9.

  PMID: 26024982 BACKGROUND

• Tang CW, Hsiao FJ, Lee PL, Tsai YA, Hsu YF, Chen WT, Lin YY, Stagg CJ, Lee IH. beta-Oscillations Reflect Recovery of the Paretic Upper Limb in Subacute Stroke. Neurorehabil Neural Repair. 2020 May;34(5):450-462. doi: 10.1177/1545968320913502. Epub 2020 Apr 23.

  PMID: 32321366 BACKGROUND

• Stancak A Jr, Pfurtscheller G. Desynchronization and recovery of beta rhythms during brisk and slow self-paced finger movements in man. Neurosci Lett. 1995 Aug 18;196(1-2):21-4. doi: 10.1016/0304-3940(95)11827-j.

  PMID: 7501247 BACKGROUND

• Stagg CJ, Bachtiar V, Johansen-Berg H. The role of GABA in human motor learning. Curr Biol. 2011 Mar 22;21(6):480-4. doi: 10.1016/j.cub.2011.01.069. Epub 2011 Mar 3.

  PMID: 21376596 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

• Pogosyan A, Gaynor LD, Eusebio A, Brown P. Boosting cortical activity at Beta-band frequencies slows movement in humans. Curr Biol. 2009 Oct 13;19(19):1637-41. doi: 10.1016/j.cub.2009.07.074. Epub 2009 Oct 1.

  PMID: 19800236 BACKGROUND

• Pfurtscheller G, Neuper C, Brunner C, da Silva FL. Beta rebound after different types of motor imagery in man. Neurosci Lett. 2005 Apr 22;378(3):156-9. doi: 10.1016/j.neulet.2004.12.034. Epub 2005 Jan 8.

  PMID: 15781150 BACKGROUND

• Pfurtscheller G, Berghold A. Patterns of cortical activation during planning of voluntary movement. Electroencephalogr Clin Neurophysiol. 1989 Mar;72(3):250-8. doi: 10.1016/0013-4694(89)90250-2.

  PMID: 2465128 BACKGROUND

• Peter J, Ferraioli F, Mathew D, George S, Chan C, Alalade T, Salcedo SA, Saed S, Tatti E, Quartarone A, Ghilardi MF. Movement-related beta ERD and ERS abnormalities in neuropsychiatric disorders. Front Neurosci. 2022 Nov 23;16:1045715. doi: 10.3389/fnins.2022.1045715. eCollection 2022.

  PMID: 36507340 BACKGROUND

• Owolabi MO, Thrift AG, Mahal A, Ishida M, Martins S, Johnson WD, Pandian J, Abd-Allah F, Yaria J, Phan HT, Roth G, Gall SL, Beare R, Phan TG, Mikulik R, Akinyemi RO, Norrving B, Brainin M, Feigin VL; Stroke Experts Collaboration Group. Primary stroke prevention worldwide: translating evidence into action. Lancet Public Health. 2022 Jan;7(1):e74-e85. doi: 10.1016/S2468-2667(21)00230-9. Epub 2021 Oct 29.

  PMID: 34756176 BACKGROUND

• Neuper C, Wortz M, Pfurtscheller G. ERD/ERS patterns reflecting sensorimotor activation and deactivation. Prog Brain Res. 2006;159:211-22. doi: 10.1016/S0079-6123(06)59014-4.

  PMID: 17071233 BACKGROUND

• Muller-Putz GR, Zimmermann D, Graimann B, Nestinger K, Korisek G, Pfurtscheller G. Event-related beta EEG-changes during passive and attempted foot movements in paraplegic patients. Brain Res. 2007 Mar 16;1137(1):84-91. doi: 10.1016/j.brainres.2006.12.052. Epub 2006 Dec 22.

  PMID: 17229403 BACKGROUND

• Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985 Jun;39(6):386-91. doi: 10.5014/ajot.39.6.386.

  PMID: 3160243 BACKGROUND

• Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res. 1981;4(4):483-92. doi: 10.1097/00004356-198112000-00001. No abstract available.

  PMID: 7333761 BACKGROUND

• Liepert J, Miltner WH, Bauder H, Sommer M, Dettmers C, Taub E, Weiller C. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neurosci Lett. 1998 Jun 26;250(1):5-8. doi: 10.1016/s0304-3940(98)00386-3.

  PMID: 9696052 BACKGROUND

• Liepert J, Bauder H, Wolfgang HR, Miltner WH, Taub E, Weiller C. Treatment-induced cortical reorganization after stroke in humans. Stroke. 2000 Jun;31(6):1210-6. doi: 10.1161/01.str.31.6.1210.

  PMID: 10835434 BACKGROUND

• Lawrence ES, Coshall C, Dundas R, Stewart J, Rudd AG, Howard R, Wolfe CD. Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population. Stroke. 2001 Jun;32(6):1279-84. doi: 10.1161/01.str.32.6.1279.

  PMID: 11387487 BACKGROUND

• Kulasingham JP, Brodbeck C, Khan S, Marsh EB, Simon JZ. Bilaterally Reduced Rolandic Beta Band Activity in Minor Stroke Patients. Front Neurol. 2022 Mar 28;13:819603. doi: 10.3389/fneur.2022.819603. eCollection 2022.

  PMID: 35418932 BACKGROUND

• Koganemaru S, Mima T, Thabit MN, Ikkaku T, Shimada K, Kanematsu M, Takahashi K, Fawi G, Takahashi R, Fukuyama H, Domen K. Recovery of upper-limb function due to enhanced use-dependent plasticity in chronic stroke patients. Brain. 2010 Nov;133(11):3373-84. doi: 10.1093/brain/awq193. Epub 2010 Aug 5.

  PMID: 20688810 BACKGROUND

• Kilavik BE, Zaepffel M, Brovelli A, MacKay WA, Riehle A. The ups and downs of beta oscillations in sensorimotor cortex. Exp Neurol. 2013 Jul;245:15-26. doi: 10.1016/j.expneurol.2012.09.014. Epub 2012 Sep 27.

  PMID: 23022918 BACKGROUND

• Joundi RA, Jenkinson N, Brittain JS, Aziz TZ, Brown P. Driving oscillatory activity in the human cortex enhances motor performance. Curr Biol. 2012 Mar 6;22(5):403-7. doi: 10.1016/j.cub.2012.01.024. Epub 2012 Feb 2.

  PMID: 22305755 BACKGROUND

• Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.

  PMID: 23785325 BACKGROUND

• Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31.

  PMID: 1135616 BACKGROUND

• Duncan PW, Bode RK, Min Lai S, Perera S; Glycine Antagonist in Neuroprotection Americans Investigators. Rasch analysis of a new stroke-specific outcome scale: the Stroke Impact Scale. Arch Phys Med Rehabil. 2003 Jul;84(7):950-63. doi: 10.1016/s0003-9993(03)00035-2.

  PMID: 12881816 BACKGROUND

• Demeyere N, Riddoch MJ, Slavkova ED, Bickerton WL, Humphreys GW. The Oxford Cognitive Screen (OCS): validation of a stroke-specific short cognitive screening tool. Psychol Assess. 2015 Sep;27(3):883-94. doi: 10.1037/pas0000082. Epub 2015 Mar 2.

  PMID: 25730165 BACKGROUND

• Chalard A, Amarantini D, Tisseyre J, Marque P, Gasq D. Spastic co-contraction is directly associated with altered cortical beta oscillations after stroke. Clin Neurophysiol. 2020 Jun;131(6):1345-1353. doi: 10.1016/j.clinph.2020.02.023. Epub 2020 Mar 19.

  PMID: 32304849 BACKGROUND

• Bachtiar V, Near J, Johansen-Berg H, Stagg CJ. Modulation of GABA and resting state functional connectivity by transcranial direct current stimulation. Elife. 2015 Sep 18;4:e08789. doi: 10.7554/eLife.08789.

  PMID: 26381352 BACKGROUND

• Bachtiar V, Johnstone A, Berrington A, Lemke C, Johansen-Berg H, Emir U, Stagg CJ. Modulating Regional Motor Cortical Excitability with Noninvasive Brain Stimulation Results in Neurochemical Changes in Bilateral Motor Cortices. J Neurosci. 2018 Aug 15;38(33):7327-7336. doi: 10.1523/JNEUROSCI.2853-17.2018. Epub 2018 Jul 20.

  PMID: 30030397 BACKGROUND

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Direct Current Stimulation; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Charlotte J Stagg, PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Catharina Zich, PhD

  University of Oxford

  STUDY DIRECTOR

Central Study Contacts

Melanie Fleming, PhD

CONTACT

+44 1865 611461; melanie.fleming@ndcn.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: There will be two experimenters: one delivering the stimulation, who will NOT be blinded and one who will be taking behavioural measures and communicating with the participant who WILL be blinded to stimulation condition.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: February 24, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 7, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: After publication of the results. There is no definitive end date

Locations

GB (1)