Clinical trial NCT02490371: Adjunct Low Frequency Repetitive Transcranial Magnetic Stimulation With Physiotherapy Enhance Upper Extremity Function Restoration
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Lead sponsor: Queen Elizabeth Hospital, Hong Kong
Sponsor class: OTHER
Collaborators: name: The Hong Kong Polytechnic University
First posted: 2015-07-03
Enrollment: 24
Sex: ALL
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Change of Cortical Excitability From Baseline to at 4th Weeksand 12th Weeks Training in Motor Evoked Potential at 120% Resting MotorThreshold at Affected Hand
timeFrame: Baseline and at 4th weeks and at 12th weeks
Secondary outcomes:
measure: Change of Upper Limb Impairment From Baseline to at 4th Weeks & 12 th Weeks Training in Fugl-Meyer Assessment (FM) Scale
timeFrame: Baseline and at 4th weeks and at 12th weeks
measure: Change of Grip Strength From Baseline to at 4th Weeks and at 12th Weeks Training in Force (Kilogram )
timeFrame: Baseline and at 4th weeks and at 12th weeks
measure: Change of Upper Limb Function From Baseline to at 4th Weeks Training in Action Research Arm Test (ARAT) Scale
timeFrame: Baseline and at 4th weeks and at 12th weeks
measure: Change of Reaction Time From Baseline to at 4th Weeks and at 12th Weeks Training in Time Measurement (Seconds)
timeFrame: Baseline and at 4th weeks and at 12th weeks
measure: Change of Health Status Measurement From Baseline to at 4th Weeks and at 12th Weeks in Stroke Impact Scale
timeFrame: Baseline and at 4th & 12 th weeks
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Queen Elizabeth Hospital
Study officials:
affiliation: Senior Physiotherapist
name: Ka yan LUK
role: PRINCIPAL_INVESTIGATOR
References: