Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201907882363035 Date of Approval: 22/07/2019
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Role of Bilateral Repetitive Transcranial Magnetic Stimulation in Stroke Patients
Official scientific title Role of Bilateral Repetitive Transcranial Magnetic Stimulation in Stroke Patients
Brief summary describing the background and objectives of the trial Background and Rationale Stroke is the major cause of disability worldwide, the most common impairment is contralateral motor disabilit.Repetitive transcranial magnetic stimulation is a noninvasive brain stimulation to the motor cortex.RTMS allows modulating cortical activity after stroke, at low frequencies (1 HZ or less), it has an inhibitory effect, whereas at high frequencies (5-25 HZ), it is able to enhance cortical excitability . Research has demonstrated that low-frequency rTMS over the unaffected hemisphere decreased the excitability of the unaffected hemisphere and improved the motor function of the paretic hand in patients after stroke (Mansur et al.,2005). High-frequency rTMS over the affected hemisphere also improved the motor function of the paretic hand by increasing the excitability of the affected motor cortex (Takeuchi et al., 2005). Considering the interhemispheric competition model of patients after stroke, adding high-frequency rTMS over the affected hemisphere along with low-frequency rTMS over the unaffected hemisphere might improve the motor function of the paretic side in the patients after stroke by a greater degree than would unilateral rTMS alone(Takeuchi et al., 2009). For continuous motor improvement, it is important to impart additional motor training while repetitive trans cranial magnetic stimulation modulates the neural network between both hemispheres and remodels work in the affected hemisphere (Takeuchi and izumi., 2012) Objectives : Evaluate the effect of bilateral rtms, appiled to the primary motor cortex (stimulatory 5HZ rtms over the affected hemisphere alternated by inhibitory 1 HZ over the non-affected hemisphere) in improvement of upper limb motor disablity due to stroke.     
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Nervous System Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Devices
Anticipated trial start date 04/04/2016
Actual trial start date 02/05/2016
Anticipated date of last follow up 01/11/2017
Actual Last follow-up date
Anticipated target sample size (number of participants) 55
Actual target sample size (number of participants) 55
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Repititive transcranial magnetic stimualtion rTMS Bilateral rtms group, patients will receive five active alternating stimulatory 5HZrtms over the affected hemisphere and inhibitory 1HZrtms over the non-affected hemipshere . 5 consective daily sessions Motor theroshold is first determined separately for each pateint . Five rTMS sessions will be done by Magstim rapid 2, over the primary motor cortex at an optimal site for the first dorsal interosseus muscle(FDI) for 5 days. After neurological Examination by NIHSS patients complaining stroke are randomly divided in to groups and rtms sessions are given. For the bilateral rTMS group , each session consisted of: One Stimulatory 5 Hz rTMS train, of 10 sec duration (50 stimuli) over the affected motor hemisphere, alternating with five trains of inhibitory 1Hz rTMS, each train 10 sec duration (50 stimuli) over the non-affected motor hemisphere.A total of twenty stimulatory trains were given alternating with a total of 100 inhibitory trains, with power intensity 90% of the motor threshold (1000 pulses over each hemisphere per session). It was difficult to apply rTMS over the affected and unaffected hemispheres simultaneously due to the mechanical limitation of the overlap of the figure-of-8 coils in the patient’s head .Follow up with improvement of the FUGL MEYER and Wolf Motor Function Test. was done before and after the sessions and after one month. All groups will receive task oriented therapy by physical therapy specialist .Exercise must be done within the sessions and for one month 3 days per week. 15
Experimental Group Repititive transcranial magnetic stimulation Stimulatory rtms group, patients will receive five active stimulatory 5HZrtms over the affected hemisphere alternating with sham inhibitory 1HZrtms over the non-affected hemipshere . 5 consecutive daily sessions Motor theroshold is first determined separately for each pateint . Five rTMS sessions will be done by Magstim rapid 2, over the primary motor cortex at an optimal site for the first dorsal interosseus muscle(FDI) for 5 days. After neurological Examination by NIHSS patients complaining stroke are randomly divided in to groups and rtms sessions are given. For the Stimulatory rTMS group , each session consisted of: One active Stimulatory 5 Hz rTMS train of 10 sec duration (50 stimuli) over the affected motor hemisphere alternating with five trains of inhibitory sham 1Hz rTMS of 10 sec duration each (50 stimuli) over the non-affected motor hemisphere. A total of active twenty stimulatory trains were given daily alternating with a total of 100 sham inhibitory trains with power intensity 90% of the motor thershold per session. Sham stimualtion was applied over the optimal site by positioning the coil perpendicular to the scalo hot spot (1000 pulses over each hemiphere per session).Follow up with improvement of the FUGL MEYER and Wolf Motor Function Test was done before, after the sessions and after one month. All groups will receive task oriented therapy by physical therapy specialist .Exercise must be done within the sessions and for one month 3 days per week. 15
Experimental Group Repititive transcranial magnetic stimualtion Inhibitory rTms : patients will receive five active inhibitory 1 Hz rTMS daily sessions over the non-affected hemisphere alternating with sham stimulatory 5 Hz rTMS over the affected hemisphere. 5 consecutive daily sessions Motor theroshold is first determined separately for each pateint . Five rTMS sessions will be done by Magstim rapid 2, over the primary motor cortex at an optimal site for the first dorsal interosseus muscle(FDI) for 5 days. After neurological Examination by NIHSS patients complaining stroke are randomly divided in to groups and rtms sessions are given. For the inhibitory rTMS group , each session consisted of: Active five trains of inhibitory 1 Hz, each train of 10 sec duration each, applied over the non-affected hemisphere (50 stimuli) alternating with one stimulatory sham 5Hz , of 10 sec duration(50 stimuli), applied over the affected hemisphere. Sham stimualtion was applied over the optimal site by positioning the coil perpendicular to the scalo hot spot.A total of 100 inhibitory active trains were given daily alternating with a total of twenty stimulatory sham trains with power intensity 90% of the motor threshold per session.(1000 pulses over each hemiphere per session) Follow up with improvement of the FUGL MEYER and Wolf Motor Function Test was done before, after the sessions and after one month. All groups will receive task oriented therapy by physical therapy specialist .Exercise must be done within the sessions and for one month 3 days per week. 15
Control Group Repititive transcranial magnetic stimulation Control Group: Ten patients received five bilateral alternating sham rTMS daily sessions (stimulatory over the affected hemisphere and inhibitory over the non-affected hemisphere) 5 consecutive daily sessions Ten patients receiving task oriented physio therapy only were scheduled to receive bilateral five sham daily sessions, each session consisited of: One sham Stimulatory 5 Hz rTMS train, of 10 sec duration (50 stimuli) over the affected motor hemisphere, alternating with five trains of sham inhibitory 1Hz rTMS, each train 10 sec duration (50 stimuli) over the non-affected motor hemisphere.A total of twenty sham stimulatory trains were given alternating with a total of 100 sham inhibitory trains, with power intensity 90% of the motor threshold (1000 pulses over each hemisphere per session).Sham stimualtion was applied over the optimal site by positioning the coil perpendicular to the scalp hot spot. Follow up with improvement of the FUGL MEYER and Wolf Motor Function test were done before, after and after one month of the sessions. 10 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Patients presenting by their first ischemic or hemorrhagic cerebrovascular stroke within >two weeks from onset so patients could have passed the flaccid stage and < six months duration of symptoms, as the best cortical plasticity is obtained in a period less than six months(Takeuchi et al., 2009). -Subcortical hemispheric stroke confirmed by magnetic resonance imaging (MRI). -Patients of a minor (1-4) to moderate (5-15) national institutes of health stroke scale score (Lyden, Lu & Levine, 2001) to allow patient to receive treatment and perform tests (Wolf Motor function test and Fugl Meyer assessment) to assess improvement with minimum assistance. -No prior experience of rTMS to confirm blindness of the intervention -Family history of epilepsy or patients who are known to be epileptic. -Pregnant females. -Convulsion after the stroke onset -Patients with any medical metal devices incompatible with transcranial magnetic stimulation (pacemaker). -Bi-hemispheric or multifocal stroke. -Premorbid lower motor neuron impairment prior to the onset of stroke like peripheral neuropathy or radiculopathy.Other comorbidities as fracture or deformity. -Patients with heart failure Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 60 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/05/2016 Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
El Manial cairo 11553 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Assesment Of bilateral rtms therapy (Stimulatory 5Hz rTMS over the affected hemisphere alternated by inhibitory 1Hz rTMS over the non-affected hemisphere) could lead to an improvement in the motor function of the paretic hand in stroke patients measured after sessions and then after one month from the sessions
Secondary Outcome improvement of post stroke spascity if present measured after sessions then after one month
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kasralainy cairo university hositals El Manial cairo 11553 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Dina El Salmawy 47 fayrouz district 6th october city cairo 12566 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Dina Ahmed El Salmawy 47 gamal abdel nasser street, fayrouz district, 6th october city cairo 12566 Egypt Individual
COLLABORATORS
Name Street address City Postal code Country
Dr.Abdulallim Atteya Faculty of physical therapy , Cairo university cairo 12611 Egypt
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ann Abdel kader Ann.abdelkader@yahoo.com 01006063114 Mohandseen,giza
City Postal code Country Position/Affiliation
cairo 12611 Egypt Professor and chairman of clinical neurophysilogy unit cairo university hospitals
Role Name Email Phone Street address
Scientific Enquiries M.Mohsen Ibrahim kasralainirec@gmail.com 01112137888 Manial street
City Postal code Country Position/Affiliation
cairo 11553 Egypt professor of cardiology cairo university kasralainy hospitals
Role Name Email Phone Street address
Public Enquiries Ahmed mowafy crc_pharma@kasralainy.edu.eg 0020253411456 Manisl street, Medical Pharmacology Department, cairo university kasralainy hospitals
City Postal code Country Position/Affiliation
cairo 11553 Egypt professor of internal medicine cairo university kasr alainy hospitals
Role Name Email Phone Street address
Scientific Enquiries Eman Maher eman_a_maher@yahoo.com 00201001291903 179 Masaken Elremaya Estesmari,Remayah Square
City Postal code Country Position/Affiliation
cairo 12561 Egypt assistant professor of clinical neurophysiology cairo university kasralainy hospitals
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Background: Repetitive transcranial magnetic stimulation(rTMS) can enhance brain plasticity after stroke thus maximizing recovery . At low frequencies rTMS has an inhibitory effect, whereas at high frequencies it has an excitatory effect.Combining both frequencies in bilateral stimulation is a new rTMS protocol under investiagtion. Purpose: To evaluate the efficacy of bilateral rTMS protocol applied to the primary motor cortex in improvement of upper limb motor disablity in stroke. Subjects and Methods: Fifty five patients with subacute stroke were divided into four groups according to r TMS protocol delivered : bilateral, inhibitory, stimualtory and control groups. All groups received concomitant task oriented physiotherapy. Before to after treatment assessment was carried twice, immedialtly after sessions and then one month later. Motor power and performance were evaluated by Fugl Meyer and Wolf motor function tests , for spasticity Ashworth scale was used and finaly for cortical excitabilty Motor evoked potentials were compared, correlations with clinical picture were done as well. Results: All groups showed significant improvement.Bilateral, Inhibitory and stimulatory groups showed nearly same efficacy but bilateral protocol was superior in spasticity.Stimulatory group effect was only over the affected hemisphere. No correlations were found between improvement and stroke duration, site and extent of neurologic deficit except for spacticity. Conclusion: Bilateral rTMS is a safe effective method to improve motor disability of paretic upper limb after stroke.Inhibitory and stimulatory rTMS showed comparable effect Study Protocol opened Key words; bilateral, repetitive trans-crainal magnetic stimulation (rTMS), stroke, cortical plasticity, task oriented physiotherapy
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information