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Repetitive Transcranial Magnetic Stimulation in Post Stroke Upper Limb Spasticity

Primary Purpose

Spasticity as Sequela of Stroke

Status
Completed
Phase
Not Applicable
Locations
Turkey
Study Type
Interventional
Intervention
Repetitive transcranial magnetic stimulation
Sponsored by
Izmir Katip Celebi University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spasticity as Sequela of Stroke focused on measuring Spasticity, Stroke, Repetitive transcranial magnetic stimulation, Premotor cortex

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • ≥ 18 years
  • Stroke history ≥ 1 year
  • Having a first stroke
  • Grade 2 or 3 muscle tone according to the Modified Ashworth Scale (MAS) assessment in at least one of the elbow, wrist and finger flexors
  • Signed consent to participate in the study

Exclusion Criteria:

  • To have a clinical condition (metallic implant, cardiac pace, pregnancy, breastfeeding, claustrophobia, epilepsy, head trauma, cranial operation history) that will constitute a contraindication to transcranial magnetic stimulation
  • Presence of malignancy
  • Pregnancy or breastfeeding
  • Non-stroke disease or lesion affecting the sensorimotor system
  • Presence of pump/shunt
  • Advanced cognitive impairment
  • To have been rehabilitated in the last 3 months
  • Botulinum toxin injection in the last 3 months
  • Taking systemic antispastic drugs (Patients taking these drugs may be included in the study after a period of at least 3 times the half-life of the drug used if they agree to quit)
  • Previously treated with TMS

Sites / Locations

  • İlker Şengül

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Sham Comparator

Arm Label

Excitatory repetitive transcranial magnetic stimulation group

Inhibitory repetitive transcranial magnetic stimulation group

Sham repetitive transcranial magnetic stimulation group

Arm Description

One session of repetitive transcranial magnetic stimulation (rTMS) treatment with 10 Hz frequency will be applied to the contralesional dorsal premotor cortex. Application will be performed with Neurosoft-Neuro MS / D device. 90% of the motor threshold will be used in the stimulation. Stimulation is planned for a total of 15 minutes and a total of 1500 beats in the form of a 5 seconds 10 Hz stimulation followed by a 25 seconds interval.

One session of repetitive transcranial magnetic stimulation (rTMS) treatment at 1 Hz frequency will be applied to the contralesional dorsal premotor cortex. Application will be performed with Neurosoft-Neuro MS / D device. 90% of the motor threshold will be used in the stimulation. Stimulation is planned for a total of 25 minutes and a total of 1500 beats in the form of 1 Hz stimulation.

Single session of sham application for a total of 25 minutes. Sham application will be performed by holding the probe of the device vertically to the vertex. The device will be operated at the lowest operating power of 1 to produce the same stimulation sounds like the active application. The device operating at this power is not likely to give any stimulation due to the probe being held upright.

Outcomes

Primary Outcome Measures

Modified Ashworth Scale
The modified Ashworth Scale is a scale that clinically evaluates the presence and severity of muscle tone increase. It is an ordinal scale that evaluates spasticity at six levels between 0 and 4 (0, 1, 1+, 2, 3, 4). The severity of spasticity increases as the score increases. Score 0 indicates no increase in muscle tone, while score 4 indicates that the affected part is rigid. Six levels between 0 and 5 (0, 1, 2, 3, 4, 5) will be used in statistical analysis. The score of 1+ will be treated as 2, 2 as 3, 3 as 4 and 4 as 5.

Secondary Outcome Measures

F wave parameters
F-wave is one of the late responses caused by antidromic stimulation of alpha motor neurons. It occurs following supramaximal electrical stimulation of peripheral motor nerves following M response. The F wave indicates the transmission from the stimulated point to the motor neuron and back to the recording electrode. Increased F wave frequency, increased F / M ratio and amplitude has been considered to indicate the increased motor neuron excitability.

Full Information

First Posted
August 16, 2019
Last Updated
March 31, 2022
Sponsor
Izmir Katip Celebi University
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1. Study Identification

Unique Protocol Identification Number
NCT04063995
Brief Title
Repetitive Transcranial Magnetic Stimulation in Post Stroke Upper Limb Spasticity
Official Title
Effect of Repetitive Transcranial Magnetic Stimulation Over Contralesional Dorsal Premotor Cortex on Post Stroke Upper Limb Spasticity
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
September 9, 2019 (Actual)
Primary Completion Date
June 27, 2021 (Actual)
Study Completion Date
June 27, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Izmir Katip Celebi University

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
The reticulospinal pathway (RSP) is at the center of spasticity mechanism. The RSP indirectly synapses with motor neurons via interneurons in the ventromedial intermediate zone in both halves of the spinal cord, and directly synapses with motor neurons of proximal extremity muscles. The main motor cortex region controlling unilateral RSP is the premotor cortex. That is, a single limb is represented in both premotor cortices. This suggests theoretically that if the corticoreticular pathway controlling RSP is modulated by dorsal premotor cortex stimulation, there may be a change in the regulation of the intraspinal network regulating the stretch reflex. Therefore, the hypothesis in this study is that the application of repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex in chronic stroke patients changes the severity of spasticity.
Detailed Description
Spasticity is a disorder characterized by increase in velocity-related muscle tone as a part of upper motor neuron syndrome. Although the mechanisms underlying stroke-related spasticity have not been fully understood, the current view is that spasticity is related to an imbalance between descending excitatory and inhibitory systems that regulate spinal stretch reflex and associated with abnormal intraspinal processes. The reticulospinal pathway (RSP) is at the center of this mechanism called cortical disinhibition. The dorsal RSP, which has an inhibitory effect on the spinal stretch reflex, originates from the medullary reticular formation and is under cortical control. In contrast to dorsal RSP, medial RSP which is not under the control of motor cortex originates from pontine reticular formation,and has an excitatory effect on spinal stretch reflex. The main motor cortex region controlling unilateral dorsal RSP is the premotor cortex. Unilateral RSP indirectly synapses with motor neurons via interneurons in the ventromedial intermediate zone in both halves of the spinal cord, and directly synapses with motor neurons of proximal extremity muscles. That is, a single limb is represented in both premotor cortices. This suggests theoretically that if the corticoreticular pathway controlling dorsal RSP is modulated by dorsal premotor cortex stimulation, there may be a change in the regulation of the intraspinal network regulating the stretch reflex. Furthermore, in stroke patients with severe motor impairment, the relationship between high cortical centers and the primary motor cortex is more in the form of facilitation rather than interhemispheric inhibition between the primary motor cortices. In other words, stimulation of one side premotor cortex may affect motor impairment and spasticity by affecting primary and high motor cortical centers of both hemispheres and both halves of the spinal cord. Therefore, the hypothesis in this study is that the application of repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex in chronic stroke patients changes the severity of spasticity. Based on this hypothesis, our aim is to investigate the effect of rTMS over the contralesional dorsal premotor cortex on the severity of spasticity in patients with chronic stroke with moderate to severe upper extremity spasticity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spasticity as Sequela of Stroke
Keywords
Spasticity, Stroke, Repetitive transcranial magnetic stimulation, Premotor cortex

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Excitatory repetitive transcranial magnetic stimulation group
Arm Type
Experimental
Arm Description
One session of repetitive transcranial magnetic stimulation (rTMS) treatment with 10 Hz frequency will be applied to the contralesional dorsal premotor cortex. Application will be performed with Neurosoft-Neuro MS / D device. 90% of the motor threshold will be used in the stimulation. Stimulation is planned for a total of 15 minutes and a total of 1500 beats in the form of a 5 seconds 10 Hz stimulation followed by a 25 seconds interval.
Arm Title
Inhibitory repetitive transcranial magnetic stimulation group
Arm Type
Experimental
Arm Description
One session of repetitive transcranial magnetic stimulation (rTMS) treatment at 1 Hz frequency will be applied to the contralesional dorsal premotor cortex. Application will be performed with Neurosoft-Neuro MS / D device. 90% of the motor threshold will be used in the stimulation. Stimulation is planned for a total of 25 minutes and a total of 1500 beats in the form of 1 Hz stimulation.
Arm Title
Sham repetitive transcranial magnetic stimulation group
Arm Type
Sham Comparator
Arm Description
Single session of sham application for a total of 25 minutes. Sham application will be performed by holding the probe of the device vertically to the vertex. The device will be operated at the lowest operating power of 1 to produce the same stimulation sounds like the active application. The device operating at this power is not likely to give any stimulation due to the probe being held upright.
Intervention Type
Device
Intervention Name(s)
Repetitive transcranial magnetic stimulation
Intervention Description
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention that uses magnetic fields to stimulate nerve cells to improve the symptoms of a variety of disorders, including stroke-related motor impairment.
Primary Outcome Measure Information:
Title
Modified Ashworth Scale
Description
The modified Ashworth Scale is a scale that clinically evaluates the presence and severity of muscle tone increase. It is an ordinal scale that evaluates spasticity at six levels between 0 and 4 (0, 1, 1+, 2, 3, 4). The severity of spasticity increases as the score increases. Score 0 indicates no increase in muscle tone, while score 4 indicates that the affected part is rigid. Six levels between 0 and 5 (0, 1, 2, 3, 4, 5) will be used in statistical analysis. The score of 1+ will be treated as 2, 2 as 3, 3 as 4 and 4 as 5.
Time Frame
Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes
Secondary Outcome Measure Information:
Title
F wave parameters
Description
F-wave is one of the late responses caused by antidromic stimulation of alpha motor neurons. It occurs following supramaximal electrical stimulation of peripheral motor nerves following M response. The F wave indicates the transmission from the stimulated point to the motor neuron and back to the recording electrode. Increased F wave frequency, increased F / M ratio and amplitude has been considered to indicate the increased motor neuron excitability.
Time Frame
Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 18 years Stroke history ≥ 1 year Having a first stroke Grade 2 or 3 muscle tone according to the Modified Ashworth Scale (MAS) assessment in at least one of the elbow, wrist and finger flexors Signed consent to participate in the study Exclusion Criteria: To have a clinical condition (metallic implant, cardiac pace, pregnancy, breastfeeding, claustrophobia, epilepsy, head trauma, cranial operation history) that will constitute a contraindication to transcranial magnetic stimulation Presence of malignancy Pregnancy or breastfeeding Non-stroke disease or lesion affecting the sensorimotor system Presence of pump/shunt Advanced cognitive impairment To have been rehabilitated in the last 3 months Botulinum toxin injection in the last 3 months Taking systemic antispastic drugs (Patients taking these drugs may be included in the study after a period of at least 3 times the half-life of the drug used if they agree to quit) Previously treated with TMS
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
İlker Şengül, M.D.
Organizational Affiliation
İzmir Katip Çelebi University
Official's Role
Principal Investigator
Facility Information:
Facility Name
İlker Şengül
City
İzmir
ZIP/Postal Code
35360
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25914638
Citation
Li S, Francisco GE. New insights into the pathophysiology of post-stroke spasticity. Front Hum Neurosci. 2015 Apr 10;9:192. doi: 10.3389/fnhum.2015.00192. eCollection 2015.
Results Reference
background
PubMed Identifier
23319482
Citation
Burke D, Wissel J, Donnan GA. Pathophysiology of spasticity in stroke. Neurology. 2013 Jan 15;80(3 Suppl 2):S20-6. doi: 10.1212/WNL.0b013e31827624a7.
Results Reference
background
PubMed Identifier
18558853
Citation
Lemon RN. Descending pathways in motor control. Annu Rev Neurosci. 2008;31:195-218. doi: 10.1146/annurev.neuro.31.060407.125547.
Results Reference
background
PubMed Identifier
16497712
Citation
Baumer T, Bock F, Koch G, Lange R, Rothwell JC, Siebner HR, Munchau A. Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways. J Physiol. 2006 May 1;572(Pt 3):857-68. doi: 10.1113/jphysiol.2006.104901.
Results Reference
background
PubMed Identifier
19833552
Citation
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
Results Reference
background
PubMed Identifier
9474057
Citation
Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. doi: 10.1016/s0168-5597(97)00096-8.
Results Reference
background
PubMed Identifier
3809245
Citation
Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987 Feb;67(2):206-7. doi: 10.1093/ptj/67.2.206.
Results Reference
background
PubMed Identifier
23094969
Citation
Wupuer S, Yamamoto T, Katayama Y, Motohiko H, Sekiguchi S, Matsumura Y, Kobayashi K, Obuchi T, Fukaya C. F-wave suppression induced by suprathreshold high-frequency repetitive trascranial magnetic stimulation in poststroke patients with increased spasticity. Neuromodulation. 2013 May-Jun;16(3):206-11; discussion 211. doi: 10.1111/j.1525-1403.2012.00520.x. Epub 2012 Oct 24.
Results Reference
background

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Repetitive Transcranial Magnetic Stimulation in Post Stroke Upper Limb Spasticity

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