NCT04063995

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Sep 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 16, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 21, 2019

Completed
19 days until next milestone

Study Start

First participant enrolled

September 9, 2019

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 27, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 27, 2021

Completed
Last Updated

April 1, 2022

Status Verified

March 1, 2022

Enrollment Period

1.8 years

First QC Date

August 16, 2019

Last Update Submit

March 31, 2022

Conditions

Keywords

SpasticityStrokeRepetitive transcranial magnetic stimulationPremotor cortex

Outcome Measures

Primary Outcomes (1)

  • 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.

    Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes

Secondary Outcomes (1)

  • F wave parameters

    Pre-intervention (baseline) and immediately after intervention (post-intervention), up to 45 minutes

Study Arms (3)

Excitatory repetitive transcranial magnetic stimulation group

EXPERIMENTAL

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.

Device: Repetitive transcranial magnetic stimulation

Inhibitory repetitive transcranial magnetic stimulation group

EXPERIMENTAL

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.

Device: Repetitive transcranial magnetic stimulation

Sham repetitive transcranial magnetic stimulation group

SHAM COMPARATOR

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.

Device: Repetitive transcranial magnetic stimulation

Interventions

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.

Excitatory repetitive transcranial magnetic stimulation groupInhibitory repetitive transcranial magnetic stimulation groupSham repetitive transcranial magnetic stimulation group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

İlker Şengül

Izmir, 35360, Turkey (Türkiye)

Location

Related Publications (9)

  • 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.

    PMID: 25914638BACKGROUND
  • 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.

    PMID: 23319482BACKGROUND
  • Lemon RN. Descending pathways in motor control. Annu Rev Neurosci. 2008;31:195-218. doi: 10.1146/annurev.neuro.31.060407.125547.

    PMID: 18558853BACKGROUND
  • 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.

    PMID: 16497712BACKGROUND
  • 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.

    PMID: 19833552BACKGROUND
  • 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.

    PMID: 9474057BACKGROUND
  • 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.

    PMID: 3809245BACKGROUND
  • 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.

    PMID: 23094969BACKGROUND
  • Sengul I, Askin A, Altun A, Tosun A. Anti-spastic effect of contralesional dorsal premotor cortex stimulation in stroke patients with moderate-to-severe spastic paresis: a randomized, controlled pilot trial. Acta Neurol Belg. 2023 Aug;123(4):1345-1354. doi: 10.1007/s13760-023-02212-2. Epub 2023 Feb 21.

MeSH Terms

Conditions

Muscle SpasticityStroke

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Muscular DiseasesMusculoskeletal DiseasesMuscle HypertoniaNeuromuscular ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • İlker Şengül, M.D.

    İzmir Katip Çelebi University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

August 16, 2019

First Posted

August 21, 2019

Study Start

September 9, 2019

Primary Completion

June 27, 2021

Study Completion

June 27, 2021

Last Updated

April 1, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations