Efficacy of rTMS and VCT on Upper Limb Function in Patients With Stroke

Efficacy of Repetitive Transcranial Magnetic Stimulation and Virtual Cycling Training on Upper Limb Function in Patients With Stroke

Stroke is the major cause of motor impairment and physical disabilities in the adult population. Spasticity and loss of dexterity are the common problems in stroke. Recently, current interventions, such as cycling training, virtual reality (VR) and repetitive transcranial magnetic stimulation (rTMS), were used for the treatment of upper extremity (UE) dysfunction in patients with stroke. However, few studies investigated the effects of the combinations of different treatment strategies using by integrating brain imaging and motor control studies. This project proposes different novel treatment strategies in the treatment of UE dysfunction in patients with stroke: combined inhibitory/facilitatory rTMS, VR-based cycling training (VCT), and combined rTMS and VCT. We hypothesize that the treatment effect of the combined protocol (optimal rTMS protocol and VCT) is more effective than single treatment due to integration of central and peripheral effects. Different treatment protocols will induce different changes in the brain reorganization and motor control, which further improve motor function, activity, participation, and health related quality of life (HRQOL).

Study Overview

• Status: Unknown
• Conditions: Cerebral Vascular Accident
• Intervention / Treatment: Device: intermittent theta burst stimulation; Device: continuous theta burst stimulation; Device: iTBS+cTBS group; Device: sham theta burst stimulation; Device: VCT; Device: VCT+optimal rTMS group

Detailed Description

This study aims to 1. identify the immediate effects of different treatment protocols in for UE training in these patients through brain image, motor control and clinical measures; 2. to determine the maintaining therapeutic effects; 3. to elucidate the most optimal treatment protocols; 4. to determine the neuro-motor control mechanism underlying clinical improvement; 5. to determine the clinimetric properties of the brain imaging and motor control measure that are responsive and valid for detecting changes after treatment protocol intervention, and 6. to identify clinical predictors influencing the outcome for treatment protocols.

The research will offer valuable motor control biomarkers for outcome prediction and targeting patients who benefit from new protocols. This project is significant for the translational and evidence-based medicine on stroke neurorehabilitation.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• first stroke
• chronic stroke (onset > 3 months)
• unilateral cerebral lesion with hemiparesis or hemiplegia
• age of 20-80 years
• no epileptic spikes on the EEG

Exclusion Criteria:

• brain stem or cerebellum stroke
• epilepsy
• aneurysm
• arteriovenous malformation
• psychiatric disease
• degenerative disease
• severe cognitive and communicative impairment or aphasia
• severe medical disease
• active medical problems
• metal implant in the body
• pregnancy
• poor cooperation with assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iTBS group; In intermittent theta burst stimulation (iTBS group), they received iTBS (80% of active motor threshold) on affected hemisphere.	Device: intermittent theta burst stimulation; In intermittent theta burst stimulation pattern (iTBS) will intermittently give a 2 s train of TBS every 10s repeated 2 times for a total of 40 times (low pulse: 1200 pulses in total) Other Names: intermittent theta burst stimulation
Experimental: cTBS group; In continuous theta burst stimulation (cTBS group), they received cTBS (80% of active motor threshold) on unaffected hemisphere.	Device: continuous theta burst stimulation; In continuous burst stimulation pattern (cTBS) will intermittently give a cTBS treatment consists of a continuous train of TBS for 40 seconds repeated for 2 times(low pulse: 1200 pulses in total). Other Names: continuous burst stimulation
Experimental: iTBS+cTBS group; Continuous theta burst stimulation (cTBS group) at first followed by intermittent theta burst stimulation (iTBS group).	Device: iTBS+cTBS group; In iTBS+cTBS pattern, continuous cTBS will be followed by intermittent iTBS (low pulse; 1200 pulses in total)
Sham Comparator: sham TBS group; In sham theta burst stimulation (sham TBS group), they received sham TBS stimulation.	Device: sham theta burst stimulation; In sham burst stimulation pattern (sham TBS) will intermittently give a sham TBS treatment consists of a continuous train of TBS for 40 seconds(almost no pulse: 1200 pulses in total). Other Names: sham theta burst stimulation
Experimental: VCT group; VCT group received the VCT training in addition to traditional rehabilitation. Each UE VCT session involved upper limb cycling training followed by UE training in addition to home program. The cycling program consisted of a warm-up exercise, twenty repetitions of hand push-up movements in the sitting position, UE cycling, and a cool-down exercise.	Device: VCT; The UE VCT programs were conducted three times per week, for 12 weeks. Each UE VCT session involved upper limb cycling training followed by UE training in addition to home program. The cycling program consisted of a warm-up exercise, twenty repetitions of hand push-up movements in the sitting position, UE cycling, and a cool-down exercise. The warm-up and cool-down exercises involved stretching and relaxing the head, neck, and the upper and lower body. Other Names: The upper extremity programs virtual cycling training program
Experimental: VCT+optimal rTMS group; VCT+optimal rTMS group received the VCT training and optimal rTMS in addition to traditional rehabilitation.	Device: VCT+optimal rTMS group; In VCT+optimal rTMS group, VCT will be combined with optimal rTMS, which has the best outcome in phase 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of mechanical measurement for stroke after 3 weeks treatment and 3 months follow-up	Kinematic analysis for upper limb	baseline, after 3 weeks of treatment, 3 months
Change from baseline of severity for stroke after 3 weeks treatment and 3 months follow-up	Brunnstrom stage classification(by severity from stage 1 to stage 6), Modified Ashworth Scale (tension of upper limb from min(0) to max (4)) and National Institute of Health Stroke Scale (severity from min(0) to max(4))	baseline, after 3 weeks of treatment, 3 months
Change from baseline of Muscle tone measurement for stroke after 3 weeks treatment and 3 months follow-up	Muscle tone	baseline, after 3 weeks of treatment, 3 months
Change from baseline of Muscle strength measurement for stroke after 3 weeks treatment and 3 months follow-up	Muscle strength	baseline, after 3 weeks of treatment, 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of body composition for stroke in after 3 weeks treatment and 3 months follow-up	InBodyS10 Body Composition Analyzer	baseline, after 3 weeks of treatment, 3 months
Change from baseline of activity for stroke in after 3 weeks treatment and 3 months follow-up	Barthel Index	baseline, after 3 weeks of treatment, 3 months
Change from baseline of ABAS for stroke in after 3 weeks treatment and 3 months follow-up	Adaptive behavior assessment system	baseline, after 3 weeks of treatment, 3 months
Change from baseline of quality of life for stroke in after 3 weeks treatment and 3 months follow-up	Stroke Impact Scale	baseline, after 3 weeks of treatment, 3 months
Change from baseline of WMFT for stroke in after 3 weeks treatment and 3 months follow-up	Wolf motor function test	baseline, after 3 weeks of treatment, 3 months
Change from baseline of MAL for stroke in after 3 weeks treatment and 3 months follow-up	Motor activity log	baseline, after 3 weeks of treatment, 3 months
Change from baseline of TUG for stroke in after 3 weeks treatment and 3 months follow-up	Timed 'Up & Go' test	baseline, after 3 weeks of treatment, 3 months
Change from baseline of FIM for stroke in after 3 weeks treatment and 3 months follow-up	Functional Independence Measure	baseline, after 3 weeks of treatment, 3 months
Change from baseline of participation for stroke in after 3 weeks treatment and 3 months follow-up	Nottingham Health Profile	baseline, after 3 weeks of treatment, 3 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Ministry of Science and Technology, Taiwan

Publications and helpful links

General Publications

• Chen YH, Chen CL, Huang YZ, Chen HC, Chen CY, Wu CY, Lin KC. Augmented efficacy of intermittent theta burst stimulation on the virtual reality-based cycling training for upper limb function in patients with stroke: a double-blinded, randomized controlled trial. J Neuroeng Rehabil. 2021 May 31;18(1):91. doi: 10.1186/s12984-021-00885-5.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): February 11, 2022
• Study Completion (Anticipated): May 31, 2022

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 17, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: randomized controlled trial; stroke; repetitive transcranial magnetic stimulation; motor control; optimal treatment protocol; VR-based cycling training (VCT); clinical predictors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 104-8816A3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No