Effects of Intermittent Theta Burst Stimulation (iTBS) on Motor Recovery of Lower Extremity in Chronic Stroke Patients

Official title

Neuroplastic Changes and Effects of Intermittent Theta Burst Stimulation (iTBS) on Motor Recovery of Upper and Lower Extremity in Chronic Stroke Patients

Overview

This study aims to evaluate the effects and clinical feasibility of non-invasive brain stimulation protocols, specifically intermittent Theta Burst Stimulation, as part of rehabilitation interventions for motor recovery of lower extremity in the chronic phase after stroke. It also seeks to explore the underlying mechanisms by investigating changes of functional and structural brain networks.

Detailed description

In this randomized control trial (RCT) group A will receive iTBS while group B will receive sham iTBS. Both groups will directly after the intervention receive 45 minutes of conventional physical therapy 3 times per week for 5 weeks, a total of 15 interventions by a blinded physiotherapist. For the iTBS intervention a Magstim Rapid² stimulator will be used also equipped with a Cadwell Sierra Summit EMG system \[for motor evoked potential (MEP) measurements\] and an ANT Visor2™ neuronavigation system \[for navigated transcranial magnetic stimulation (TMS) interventions\]. The iTBS parameters that will be used are: 600 pulses under 190 seconds at 80 % of Active Motor Threshold (AMT). The contralesional cerebellum will be targeted. The participants and clinical assessors will be blinded to the intervention.

All the patients will undergo advanced neuroimaging examinations before and after the intervention period. The exams will be then compared to identify neuroplastic changes in brain circuits.

Interventions

• Device Intermittent Theta Burst Stimulation
  iTBS protocol: 600 pulses at 80% of AMT for 190 sec on the contralesional cerebellum, targeted with the support of a neuronavigational system, 15 sessions over a period of 5 weeks
• Device Sham Intermittent Theta Burst Stimulation
  It is identical to its active version, replicates operational sounds, and delivers a very shallow magnetic field to mimic the sensation of magnetic stimulation.

Primary outcome measures

• miniBest test [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]

Secondary outcome measures (12)

• Fugl-Meyer Assessment - Lower Extremity [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Modified Ashworth Scale (MAS) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Neuroflexor [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Lower Extremity Motor Coordination Test (LEMOCOT) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• 6 minutes walk test [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Functional Ambulation Categories (FAC) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Falls Efficacy Scale Swedish version (FES-S) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Walking impact scale (MSWS-12 S) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Canadian Occupational Performance Measure [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Montreal Cognitive Assessment (MoCA) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Stroke Impact Scale (SIS) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Motor Evoked Potentials (MEPs) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]

Eligibility criteria

Inclusion criteria

• Age over 18
• Chronic stroke (>6 months)
• Residual hemiparesis FAC ≥3

Exclusion criteria

• Metal implants
• Epilepsy/seizures
• Pregnancy
• Claustrophobia (related to MRIs exams)
• Severe cognitive impairment
• Untreated or unstable depression/anxiety
• Other disabilities prohibiting intensive physical training

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Sweden · 1 center

• Department of Rehabilitation Medicine, Danderyd Hospital, Danderyd, Stockholm 18288 — Stockholm

Publications

• Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci. 2006 Jul;7(7):511-22. doi: 10.1038/nrn1953. PMID 16791141
• Wang J, Wu Z, Hong S, Ye H, Zhang Y, Lin Q, Chen Z, Zheng L, Qin J. Cerebellar transcranial magnetic stimulation for improving balance capacity and activity of daily living in stroke patients: a systematic review and meta-analysis. BMC Neurol. 2024 Jun 15;24(1):205. doi: 10.1186/s12883-024-03720-1. PMID 38879485
• Wang C, Zhang Q, Zhang L, Zhao D, Xu Y, Liu Z, Wu C, Wu S, Yong M, Wu L. Comparative efficacy of different repetitive transcranial magnetic stimulation protocols for lower extremity motor function in stroke patients: a network meta-analysis. Front Neurosci. 2024 Feb 15;18:1352212. doi: 10.3389/fnins.2024.1352212. eCollection 2024. PMID 38426021
• Koch G, Bonni S, Casula EP, Iosa M, Paolucci S, Pellicciari MC, Cinnera AM, Ponzo V, Maiella M, Picazio S, Sallustio F, Caltagirone C. Effect of Cerebellar Stimulation on Gait and Balance Recovery in Patients With Hemiparetic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2019 Feb 1;76(2):170-178. doi: 10.1001/jamaneurol.2018.3639. PMID 30476999
• Jiang T, Wei X, Wang M, Xu J, Xia N, Lu M. Theta burst stimulation: what role does it play in stroke rehabilitation? A systematic review of the existing evidence. BMC Neurol. 2024 Feb 1;24(1):52. doi: 10.1186/s12883-023-03492-0. PMID 38297193
• Fan H, Song Y, Cen X, Yu P, Biro I, Gu Y. The Effect of Repetitive Transcranial Magnetic Stimulation on Lower-Limb Motor Ability in Stroke Patients: A Systematic Review. Front Hum Neurosci. 2021 Sep 1;15:620573. doi: 10.3389/fnhum.2021.620573. eCollection 2021. PMID 34539362
• Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, PMID 25034472
• Christiansen MG, Senko AW, Anikeeva P. Magnetic Strategies for Nervous System Control. Annu Rev Neurosci. 2019 Jul 8;42:271-293. doi: 10.1146/annurev-neuro-070918-050241. Epub 2019 Apr 2. PMID 30939100

Identifiers

NCT: NCT07073235 · iTBS-study lower extremity

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗