Efficacy of Integrated Therapy of rTMS and rPMS on Upper Limb Function in Patients With Stroke

Not Applicable

• Conditions: Stroke
• Interventions: Device: rTMS+rPMS_cTBS_R; Device: rTMS +sham-rPMS; Device: rTMS + optimal-rPMS; Device: rTMS+rPMS_iTBS_M/U; Device: rTMS+rPMS_iTBS_R; Device: sham-rTMS+sham-rPMS; Device: rTMS+rPMS_cTBS_M/U; Device: sham-rTMS+optimal-rPMS

• Registration Number: NCT04265365
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

Repetitive transcranial magnetic stimulation (rTMS) and repetitive peripheral magnetic stimulation (rPMS) are innovative treatments for patients with stroke. Therefore, the integrated therapy of rTMS and with repetitive peripheral magnetic stimulaiton (rPMS) is employed in this project. This proposal aims at exploring different novel treatment strategies in the treatment of UE dysfunction in patients with stroke: rTMS integrated with rPMS.

Detailed Description

Several aims in this study include identifying a better protocol of rPMS with Theta burst stimulation (TBS) and different nerves stimulation location, identifying the most optimal treatment protocols for rPMS (TBS treatment and nerve stimulation location), integrating novel treatment protocol (optimal rTMS + rPMS), comparing efficacy between integrated therapy of optimal rTMS and rPMS treatment and single rTMS or rPMS treatment, determining the mechanism of neuro-motor control, clinical predictors, and related biomarkers for the novel treatment protocol A total of 108-135 patients with stroke will be recruited. During phase 1 (year 1 and year 2), 72 to 90 participants will be randomly enrolled in different groups (12-15 participants in each group). For the first year, the participants will be randomly enrolled in 3 different groups according to the TBS mode (iTBS vs.cTBS). In the second year, the participants will be randomly enrolled in 3 different groups according to the stimulated nerves (radial, median/ulnar nerves) to find the optimal novel treatment protocols for UE dysfunction in patients with stroke. During phase 2 (2-3 years), 36 to 45 patients will be randomly enrolled into 3 groups of rTMS and rPMS integrated therapy to identify optimal integrated novel treatment protocol.

Outcome measures include clinical based on International Classification of Functioning, Disability and Health (ICF) and motor control (Motor Evoked Potential, MEP; muscle tone assessment (MYOTON); pinch and grip strength and kinematics of upper extremity) assessments that administered at pretest, posttest, and 3-month follow-up. The aim of this study is to establish the novel assessment and treatment protocols in patients with stroke. The intervention will be conducted 10 times in 2 weeks (five times per week). The optimal effective treatment protocol of combination of rTMS and rPMS will also be established. The results of this study will be applied to the translational and evidence-based medicine of the neuro-rehabilitation field of stroke research.

Study Timeline

• Study Start: 2019-02-27
• Study First Submitted: 2020-02-02
• Study First Submitted QC: 2020-02-09
• Study First Posted: 2020-02-11
• Status Verified: 2021-07
• Last Update Submitted: 2022-03-07
• Last Update Posted: 2022-03-09
• Primary Completion: 2022-12-11
• Study Completion: 2023-02-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• first stoke and in stable phase
• age 20-80 years
• unilateral brain lesions with unilateral hemiplegia
• brain wave examination without epileptic waves

Exclusion Criteria

• brain stem or cerebellar stroke
• Patients with epilepsy
• Patients with aneurysm or cerebrovascular malformation
• Patients with mental illness
• Patients with degenerative diseases (such as neurodegenerative diseases)
• Patients with severe intelligence or language barriers (such as mental retardation or severe communication impairment)
• Patients with serious medical conditions (such as heart failure)
• Patients with acute disease (such as infection)
• Patients had metal implants in the body (such as cardiac rhythm or brain metal implants, metal clips for aneurysms)
• Patients had botox injection or surgery in the first half of the study
• pregnant woman or breastfeeding woman
• other obstacles (such as claustrophobia, obesity, etc.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
rTMS+rPMS_cTBS_R	rTMS+rPMS_cTBS_R	In this group, they received intermittent theta burst stimulation on affected hemisphere after following continuous theta burst stimulation(cTBS) at radial nerve on affected hand.
rTMS +sham-rPMS	rTMS +sham-rPMS	In this group, they received iTBS on affected hemisphere after following sham TBS stimulation at radial nerve on affected hand.
rTMS + optimal-rPMS	rTMS + optimal-rPMS	In this group, patient received iTBS on affected hemisphere after following optimal repetitive peripheral magnetic stimulation(rPMS) on affected hand.
rTMS+rPMS_iTBS_M/U	rTMS+rPMS_iTBS_M/U	In this group, they received iTBS on affected hemisphere after following iTBS at median/ulnar nerve on affected hand.
rTMS+rPMS_iTBS_R	rTMS+rPMS_iTBS_R	In this group, they received intermittent theta burst stimulation(iTBS) on affected hemisphere after following iTBS at radial nerve on affected hand.
sham-rTMS+sham-rPMS	sham-rTMS+sham-rPMS	In this group, they received iTBS on affected hemisphere after following sham TBS stimulation at median/ulnar nerve on affected hand.
rTMS+rPMS_cTBS_M/U	rTMS+rPMS_cTBS_M/U	In this group, they received iTBS on affected hemisphere after following cTBS at median/ulnar nerve on affected hand.
rTMS+ sham-rPMS	rTMS +sham-rPMS	In this group, patient received iTBS on affected hemisphere after following sham repetitive peripheral magnetic stimulation on affected hand.
sham-rTMS+optimal-rPMS	sham-rTMS+optimal-rPMS	In this group, patient received sham iTBS on affected hemisphere after following optimal repetitive peripheral magnetic stimulation on affected hand.

Primary Outcome Measures

Name	Time	Method
Change from baseline Fugl Meyer Assessment at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Fugl Meyer Assessment is used to measure upper and lower extremity motor , range of motion, sensation, pain and balance.
Change from baseline Motor evoked potential at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The comparison of baseline of Motor Evoked Potential for stroke after different therapy, including resting motor threshold (RMT), active motor thresholds (AMT), input-output curve (IO curve) and stationary period.
Change from baseline Brunnstrom stage at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Brunnstrom stage is used to classify the severity of stroke patient according to specific movement.
Change from baseline Modified Ashworth Scale at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Modified Ashworth Scale is used to measure the muscle tone of affected limb, for each item minimum value is 0 and maximum value is 4, higher scores mean a worse outcome.
Change from baseline Motion analysis at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	All participants will be instructed to perform a series of upper-extremity tasks. The tasks include reaching and grasping. An 7-camera motion analysis system (Vicon system, 3-D Oxfort Metrics Ltd, Oxford, UK) is used in conjunction with a personal computer to capture the movement of markers placed on the participant's body; analog signals were collected simultaneously. Movements were recorded at 120 Hz and digitally low-pass filtered at 5 Hz using a second-order Butterworth filter. Reference markers are placed on the distal interphalangeal joints of the thumb and index finger, the styloid process of the ulna, proximal end of the second metacarpal, and the object.
Change from baseline Muscle strength at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The comparison of baseline of Muscle strength for stroke after different therapy, including lateral pinch, palmar pinch, and tip pinch.
Change from baseline Myoton at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The comparison of baseline of Myoton for stroke after different therapy, assessing the functional status of skeletal muscle.

Secondary Outcome Measures

Name	Time	Method
Change from baseline Action Research Arm Test at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Action Research Arm Test is used to measure bilateral gross manual and finger dexterity.
Change from baseline Nine-Hole test at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Nine-Hole Peg Test (NHPT) is used to measure finger dexterity in patients with various neurological diagnoses.
Change from baseline Box and Block Test at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Box and Block Test (BBT) measures unilateral gross manual dexterity.
Change from baseline Stroke Impact Scale at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Stroke Impact Scale(SIS) is used to measure the influence of several aspects after stroke, for each item minimum value is 1 and maximum value is 5, higher scores mean a better outcome.
Change from baseline Jebson Taylor Hand Function Test at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Jebson Taylor Hand Function Test (JTHFT) is used to assess a broad range of unilateral hand functions required for activities of daily living(ADLs).
Change from baseline Functional Independence Measure at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The purpose of Functional Independence Measure(FIM) is to understand and track adult's life function performance, progress and goal achievement. There are three main areas: self-care, mobility, and cognition. The score is from 1 to 7 points, 1 is completely dependent, and 7 is completely independent.
Change from baseline Motor Activity Log at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Motor Activity Log(MAL) is used to measure the quality and quantity of a stroke patient when performing activities using the affected hand.
Change from baseline Wolf Motor Function Test at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Wolf Motor Function Test(WMFT) is used to measure unilateral motor quality and strength.
Change from baseline Nottingham Health Profile at after six weeks of treatment and three month	baseline, after 6 weeks of treatment, 3 months	The Nottingham Health Profile(NHP) is a questionnaire that assesses the quality of life associated with health. There are a total of 38 items, divided into six sub-items: mobility, social isolation, emotional response, pain, sleep and energy.

Trial Locations

Locations (1)

Chang Gung Memoria Hospital; 🇨🇳 Taoyuan, Taiwan