Effects of Intermitted Theta Burst Stimulation (iTBS) on Motor Recovery of Upper 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 upper 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 controlled 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 ipsilesional motor cortex 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 ipsilesional motor cortex, 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

• Fugl-Meyer Assessment - Upper Extremity [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)

• 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.]
• Box and Block Test (BBT) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Action Research Arm Test (ARAT) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Dextrain Manipulandum™ [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Hand-held Dynamometer/Grip Strength [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Purdue Pegboard Test (PPT) [Time frame: At baseline, after completion of the 5 week intervention to assess change as well at 12 weeks follow up.]
• Visuomotor force tracking [Time frame: At baseline and after completion of the 5 week intervention and at the 12 weeks follow up, to assess changes]
• 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.]
• 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.]
• Stroke Impact Scale (SIS) [Time frame: At baseline and after completion of the 5 week intervention and at the 12 weeks follow up, to assess changes]
• 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 FM-UE>17

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, Stock — Stockholm

Publications

• Lemon RN. Descending pathways in motor control. Annu Rev Neurosci. 2008;31:195-218. doi: 10.1146/annurev.neuro.31.060407.125547. PMID 18558853
• Zhang JJ, Bai Z, Fong KNK. Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial. Stroke. 2022 Jul;53(7):2171-2181. doi: 10.1161/STROKEAHA.121.037870. Epub 2022 Mar 23. PMID 35317611
• Zhang JJ, Sui Y, Sack AT, Bai Z, Kwong PWH, Sanchez Vidana DI, Xiong L, Fong KNK. Theta burst stimulation for enhancing upper extremity motor functions after stroke: a systematic review of clinical and mechanistic evidence. Rev Neurosci. 2024 Apr 29;35(6):679-695. doi: 10.1515/revneuro-2024-0030. Print 2024 Aug 27. PMID 38671584
• 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
• van Lieshout ECC, van der Worp HB, Visser-Meily JMA, Dijkhuizen RM. Timing of Repetitive Transcranial Magnetic Stimulation Onset for Upper Limb Function After Stroke: A Systematic Review and Meta-Analysis. Front Neurol. 2019 Dec 3;10:1269. doi: 10.3389/fneur.2019.01269. eCollection 2019. PMID 31849827
• 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
• 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

Identifiers

NCT: NCT07073248 · iTBS-study upper extremity

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗