Adjunct Low Frequency Repetitive Transcranial Magnetic Stimulation With Physiotherapy Enhance Upper Extremity Function Restoration

The Effectiveness of Combination of Low Frequency Repetitive Transcranial Magnetic Stimulation With Structured Physiotherapy Training Program on Restoring Upper Extremity Function for Patients After Stroke

Stroke is the leading cause of function disability or impairment. Non-promising functional return from upper limb rehabilitation has been reported. With the technology advances, transcranial magnetic stimulation (TMS), which is a form of non-invasive direct brain stimulation, may act as an attenuator in regulating or modulating the cortical excitability in order to facilitate cortical re-organization and enhance behavioral performance. Various therapeutic exercise protocols have been investigated regarding their efficacy in promoting motor recovery of the affected upper limb for patients after stroke and the preliminary results were supportive. However, limited numbers of randomized control clinical trials have been published in investigating the "priming" or "additive" value of low frequency repetitive TMS (rTMS) with combination of structural motor training programs.

Thus the objective of this study is: to determine the effectiveness of the combination of low frequency rTMS on contra-lesional M1 and a structured upper limb motor training program on restoring upper limb function among patients with stroke in sub-acute stage. It is hypothesized that the rTMS, when combined with a structured motor training program, confers additional therapeutic effects on upper limb motor function in subacute stroke patients, when compared with the motor training program alone.

The objectives of this study is to determine the effectiveness of the combination of low frequent rTMS on contra-lesional M1 and a structured upper limb motor training program in restoring upper limb function among patients with subacute stroke.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Low frequency rTMS; Behavioral: structured physiotherapy upper limb training

Detailed Description

The proposed study will be a randomized double-blinded controlled trial. 26 stroke patients with upper limb impairment who are receiving the outpatient physiotherapy service at the Queen Elizabeth Hospital and fulfill the eligibility criteria will be recruited and randomized into two interventional groups: (1) rTMS + exercise (rTMS-Ex) group and (2) Placebo rTMS +exercise (Placebo-Ex) group. Both rTMS-Ex and placebo-Ex group will receive 10 consecutive treatment sessions (5 sessions per week), which consists of real rTMS stimulation (rTMS-ex group) or placebo rTMS (placebo-Ex group), followed by 30-minute structured upper limb strengthening and task-specific motor training program. After 2 weeks of brain stimulation and motor training, both groups will continue with the same structured motor training program for another 10 weeks (2 sessions/ week).

1. rTMS-Ex Group 10 consecutive sessions (5 days per week for 2 weeks) of 1 Hz low frequency repetitive transcranial magnetic stimulation over contra-lesional M1 region for 1200 pulse (20 minutes) at 90% motor threshold and immediately followed by 75 minutes structured physiotherapy upper limb training.

   After the 10 sessions of brain stimulation, the 30-minute structured physiotherapy upper limb training program will continue for another 12 weeks (2 sessions per week)

2. Placebo-Ex Group 10 consecutive sessions (5 sessions per week for 2 weeks) of placebo stimulation over contra-lesional M1 region and immediately followed by 30 minutes of structured physiotherapy upper limb training.

Then, the structured physiotherapy upper limb training will continue for another 12 weeks (2 sessions per week).

Evaluation on impairment level, motor performance, physiological measurements and self -perceived disability will be performed at 4 time points: before treatment (T0), immediately after treatment (T1), one-month follow-up (T2) and three-month follow-up (T3). 2-way repeated measures ANOVA will be used to determine whether the rTMS-ex group leads to better outcomes than the placebo-ex group.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Queen Elizabeth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. First-ever stroke
2. Age >60
3. muscle strength > grade 2 and < grade 5 based on manual muscle testing of hand / fingers of the affected upper limb
4. > 1 month and < 6 months after the onset of stroke

Exclusion Criteria:

1. Substantial cognitive impairment with Mini Mental State Test >24
2. Diagnosis of mental illness
3. Pathological conditions referred to as contra-indications for rTMS in guideline suggested by Wassermann (eg. Cardiac pacemaker, intracranial implants, implanted medication pumps, epilepsy)
4. Unstable cardio-pulmonary conditions -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (1) rTMS- PT Ex Group; 1 Hz low frequency rTMS over contra-lesional M1 region for 1200 pulse (20 minutes) at 90% resting motor threshold (rMT) will conduct for 10 consecutive sessions (5 days per week for 2 weeks) and immediately followed by 30- minutes structured physiotherapy upper limb training. After the 10 sessions of brain stimulation, the 30-minute structured physiotherapy upper limb training program will continue for another 12 weeks (2 sessions per week)	Device: Low frequency rTMS; 1 Hz low frequency rTMS over contra-lesional M1 region for 1200 pulse at 90% resting motor threshold for 10 sessions.Patients in the rTMS-ex group will receive the experimental rTMS A Magstim Rapid Stimulator (Magstim Company, Whitland, UK) equipped with an air-cooled figure-of-eight coil (each loop 70 mm in diameter) and neuro-navigation system will be used to deliver the intervention.; Behavioral: structured physiotherapy upper limb training; Structural Physiotherapy upper limb training for 30-minutes
Placebo Comparator: (2) Placebo- PT Ex Group; placebo stimulation over contra-lesional M1 region will be conducted for 10 consecutive sessions (5 sessions per week for 2 weeks) of and immediately followed by 30- minutes of structured physiotherapy upper limb training. Then, the structured physiotherapy upper limb training will continue for another 12 weeks (2 sessions per week).	Device: Low frequency rTMS; 1 Hz low frequency rTMS over contra-lesional M1 region for 1200 pulse at 90% resting motor threshold for 10 sessions.Patients in the rTMS-ex group will receive the experimental rTMS A Magstim Rapid Stimulator (Magstim Company, Whitland, UK) equipped with an air-cooled figure-of-eight coil (each loop 70 mm in diameter) and neuro-navigation system will be used to deliver the intervention.; Behavioral: structured physiotherapy upper limb training; Structural Physiotherapy upper limb training for 30-minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Cortical Excitability From Baseline to at 4th Weeksand 12th Weeks Training in Motor Evoked Potential at 120% Resting MotorThreshold at Affected Hand	Electromyographic (EMG) activity in first doral interossei measured at 120% resting motor threshold. The motor evoked potential amplitude will be measured peak to peak in millivolt(mV). Higher value mean better control	Baseline and at 4th weeks and at 12th weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Upper Limb Impairment From Baseline to at 4th Weeks & 12 th Weeks Training in Fugl-Meyer Assessment (FM) Scale	Fugl-Meyer Assessment (FM) scale is a stroke-specific, performance-based impairment index, the scale range from 0 to 66. 25 test items included measurement of movement, coordination, and reflex action of the different parts of the paretic upper extremity. The score could range from 0 to 66. Better motor function was reflected by a higher FMA score	Baseline and at 4th weeks and at 12th weeks
Change of Grip Strength From Baseline to at 4th Weeks and at 12th Weeks Training in Force (Kilogram )	Isometric hand grip strength will be measured using the hand-held dynamometer in kilogram (kg). Higher value reflect better hand grip strength	Baseline and at 4th weeks and at 12th weeks
Change of Upper Limb Function From Baseline to at 4th Weeks Training in Action Research Arm Test (ARAT) Scale	The 19-item Action Research Arm Test has four subscales that assess various aspects of upper limb function (i.e., pinch, grip, grasp, and gross motor). Each item was rated on a 4-point scale from 0 to 3. Scale from 0 to 57.A higher score was indicative of better upper limb function.	Baseline and at 4th weeks and at 12th weeks
Change of Reaction Time From Baseline to at 4th Weeks and at 12th Weeks Training in Time Measurement (Seconds)	A simple reaction time will be recorded through a computer system. Time for the patient to reaction to the signal will be measured in seconds (sec). Shorter period of time reflect better reaction time.Lower score means better result	Baseline and at 4th weeks and at 12th weeks
Change of Health Status Measurement From Baseline to at 4th Weeks and at 12th Weeks in Stroke Impact Scale	The 59-item Stroke Impact Scale (SIS) is a stroke-specific, self-report, health status measure. Total range from 0 to 100. Higher score reflect better result.	Baseline and at 4th & 12 th weeks

Collaborators and Investigators

• Sponsor: Queen Elizabeth Hospital, Hong Kong
• Collaborators: The Hong Kong Polytechnic University
• Investigators: Principal Investigator: Ka yan LUK, Senior Physiotherapist

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: May 31, 2015
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 3, 2015

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: PT-2015-QEHHK

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
• product manufactured in and exported from the U.S.: No