Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Post-Stroke Spasticity

NCT02268461 | Completed Results DMC FDA Device

• 1 other identifier: 1408M53261
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Spasticity is a common complication of stroke affecting quality of life. Spasticity involves exaggerated stretch reflexes that create stiffness in muscles with associated loss of motion and functional control. Traditional treatments involve range of motion, medications, and sometimes surgery. Each of these has its own limitations, which has invited exploration of alternative modes of treatment. One such treatment with the potential to benefit spasticity is repetitive Transcranial Magnetic Stimulation (rTMS). The purpose of this study is to determine whether patients with upper limb spasticity as a consequence of a chronic stroke can benefit from stimulation of the non-affected hemisphere of the brain with low-frequency (inhibitory) repetitive Transcranial Magnetic Stimulation (rTMS), potentially leading to a reduction of spasticity and clinical improvement in upper limb function.

Conditions

Spasticity

Keywords

Post-Stroke Spasticity

Outcome Measures

Primary Outcomes (2)

• Change From Baseline Contralesional Corticospinal Excitability

  Motor evoked potentials (MEPs) were measured using surface EMG. The average amplitude of 10 MEPs measured at baseline was compared to the average of 10 MEPs measured at post-test and this difference is recorded as the change in corticospinal excitability. A greater negative value would indicate larger post-test MEPs and increased corticospinal excitability.

  From Day 1 to Day 5

• Change From Baseline Finger Tracking Score

  An electrogoniometer attached to the hand was used to measure index finger movement. Patients tracked a sine wave that ranged from 85% to 15% of their individual max range of motion which does impact the accuracy measure scale. Accuracy of tracking along with the target waveform was assessed on a scale ranging from -100 to 100 (100 being perfect accuracy).

  From Day 1 to Day 5

Secondary Outcomes (2)

• Change in Stroke Impact Scale

  From Day 1 to Day 5

• Change From Baseline Resting Motor Threshold

  From Day 1 to Day 5

Study Arms (2)

rTMS then Sham rTMS

ACTIVE COMPARATOR

repetitive Transcranial Magnetic Stimulation (rTMS)

Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Sham rTMS then Real rTMS

SHAM COMPARATOR

Sham repetitive Transcranial Magnetic Stimulation (Sham rTMS)

Device: Sham repetitive Transcranial Magnetic Stimulation

Interventions

repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

The treatment arm will consist of 3 daily treatment sessions. One treatment session in this study with real rTMS will consist of 600 pulses of 1Hertz rTMS at an intensity of 90% of resting motor threshold (duration 10 minutes) applied to the primary motor area of the contralesional hemisphere.

Also known as: Magstim 200^2 Magnetic Stimulator (MODEL 3010-00), Magstim Rapid^2 Magnetic Stimulator (MODE 3004-000)

rTMS then Sham rTMS

Sham repetitive Transcranial Magnetic Stimulation DEVICE

Sham rTMS utilizes a coil that produces identical noise and tactile sensation to the real coil, but does not emit a magnetic field (0% intensity). Duration and frequency of auditory and tactile stimulation will be identical to the real intervention.

Sham rTMS then Real rTMS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• first-time stroke
• stroke at least six months prior to onset of study with chronic sequela of spasticity
• stroke location- either cortical or subcortical
• stroke type- either hemorrhagic or ischemic
• stroke hemisphere- either left or right, dominant or non- dominant hemisphere
• years of age or older
• gender- either male or female
• ability to follow three-step directions
• demonstration of 10 degrees of active extension at the metacarpophalangeal joint and wrist of the paretic upper extremity
• demonstration of consistent resting motor evoked potential from ipsilesional and contralesional hemispheres
• sufficient ambulation or wheelchair mobility to allow subject to present to treatment and testing areas with minimum assist

You may not qualify if:

• history of seizure within the past two years
• inability to follow three-step directions
• anosognosia
• moderate to severe receptive aphasia
• inability to give informed consent
• premorbid spasticity or neurologic impairment prior to stroke
• co-morbidities impairing upper extremity function such as fracture or deformity
• indwelling metal or medical devices incompatible with TMS
• pregnancy
• bi-hemispheric or multifocal stroke
• dementia
• neurolytic injection within the 3 months prior to onset of study or planned neurolytic injection during study period
• planned vacation or travel during study period

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota, Clinical and Translational Science Institute

Minneapolis, Minnesota, 55414, United States

Location

Related Publications (24)

• Carmichael ST, Tatsukawa K, Katsman D, Tsuyuguchi N, Kornblum HI. Evolution of diaschisis in a focal stroke model. Stroke. 2004 Mar;35(3):758-63. doi: 10.1161/01.STR.0000117235.11156.55. Epub 2004 Feb 12.

  PMID: 14963280 BACKGROUND

• Duque J, Murase N, Celnik P, Hummel F, Harris-Love M, Mazzocchio R, Olivier E, Cohen LG. Intermanual Differences in movement-related interhemispheric inhibition. J Cogn Neurosci. 2007 Feb;19(2):204-13. doi: 10.1162/jocn.2007.19.2.204.

  PMID: 17280510 BACKGROUND

• Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004 Mar;55(3):400-9. doi: 10.1002/ana.10848.

  PMID: 14991818 BACKGROUND

• Kirton A, Chen R, Friefeld S, Gunraj C, Pontigon AM, Deveber G. Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Lancet Neurol. 2008 Jun;7(6):507-13. doi: 10.1016/S1474-4422(08)70096-6. Epub 2008 May 1.

  PMID: 18455961 BACKGROUND

• Grefkes C, Nowak DA, Wang LE, Dafotakis M, Eickhoff SB, Fink GR. Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling. Neuroimage. 2010 Mar;50(1):233-42. doi: 10.1016/j.neuroimage.2009.12.029. Epub 2009 Dec 18.

  PMID: 20005962 BACKGROUND

• Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project. BMJ. 1997 Dec 13;315(7122):1582-7. doi: 10.1136/bmj.315.7122.1582.

  PMID: 9437276 BACKGROUND

• Carey JR, Kimberley TJ, Lewis SM, Auerbach EJ, Dorsey L, Rundquist P, Ugurbil K. Analysis of fMRI and finger tracking training in subjects with chronic stroke. Brain. 2002 Apr;125(Pt 4):773-88. doi: 10.1093/brain/awf091.

  PMID: 11912111 BACKGROUND

• Carey JR, Evans CD, Anderson DC, Bhatt E, Nagpal A, Kimberley TJ, Pascual-Leone A. Safety of 6-Hz primed low-frequency rTMS in stroke. Neurorehabil Neural Repair. 2008 Mar-Apr;22(2):185-92. doi: 10.1177/1545968307305458. Epub 2007 Sep 17.

  PMID: 17876070 BACKGROUND

• Kakuda W, Abo M, Momosaki R, Yokoi A, Fukuda A, Ito H, Tominaga A, Umemori T, Kameda Y. Combined therapeutic application of botulinum toxin type A, low-frequency rTMS, and intensive occupational therapy for post-stroke spastic upper limb hemiparesis. Eur J Phys Rehabil Med. 2012 Mar;48(1):47-55. Epub 2011 Nov 9.

  PMID: 22071503 BACKGROUND

• Kakuda W, Abo M, Kobayashi K, Momosaki R, Yokoi A, Fukuda A, Ito H, Tominaga A, Umemori T, Kameda Y. Anti-spastic effect of low-frequency rTMS applied with occupational therapy in post-stroke patients with upper limb hemiparesis. Brain Inj. 2011;25(5):496-502. doi: 10.3109/02699052.2011.559610.

  PMID: 21456998 BACKGROUND

• Kakuda W, Abo M, Kobayashi K, Momosaki R, Yokoi A, Fukuda A, Ishikawa A, Ito H, Tominaga A. Low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for poststroke patients with upper limb hemiparesis: preliminary study of a 15-day protocol. Int J Rehabil Res. 2010 Dec;33(4):339-45. doi: 10.1097/MRR.0b013e32833cdf10.

  PMID: 20613547 BACKGROUND

• Kirton A, Deveber G, Gunraj C, Chen R. Cortical excitability and interhemispheric inhibition after subcortical pediatric stroke: plastic organization and effects of rTMS. Clin Neurophysiol. 2010 Nov;121(11):1922-9. doi: 10.1016/j.clinph.2010.04.021.

  PMID: 20537584 BACKGROUND

• Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD. Corticocortical inhibition in human motor cortex. J Physiol. 1993 Nov;471:501-19. doi: 10.1113/jphysiol.1993.sp019912.

  PMID: 8120818 BACKGROUND

• Liepert J, Storch P, Fritsch A, Weiller C. Motor cortex disinhibition in acute stroke. Clin Neurophysiol. 2000 Apr;111(4):671-6. doi: 10.1016/s1388-2457(99)00312-0.

  PMID: 10727918 BACKGROUND

• Mally J, Dinya E. Recovery of motor disability and spasticity in post-stroke after repetitive transcranial magnetic stimulation (rTMS). Brain Res Bull. 2008 Jul 1;76(4):388-95. doi: 10.1016/j.brainresbull.2007.11.019. Epub 2007 Dec 26.

  PMID: 18502315 BACKGROUND

• Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985 Jun;39(6):386-91. doi: 10.5014/ajot.39.6.386.

  PMID: 3160243 BACKGROUND

• Mathiowetz V, Federman S, Wiemer, D. Box and Block Test of Manual Dexterity: Norms for 6-19 Year Olds. CJOT. 1985b; 52(5): 241-245.

  BACKGROUND

• McDonnell MN, Orekhov Y, Ziemann U. The role of GABA(B) receptors in intracortical inhibition in the human motor cortex. Exp Brain Res. 2006 Aug;173(1):86-93. doi: 10.1007/s00221-006-0365-2. Epub 2006 Feb 18.

  PMID: 16489434 BACKGROUND

• Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):e2-e220. doi: 10.1161/CIR.0b013e31823ac046. Epub 2011 Dec 15. No abstract available.

  PMID: 22179539 BACKGROUND

• Sommerfeld DK, Gripenstedt U, Welmer AK. Spasticity after stroke: an overview of prevalence, test instruments, and treatments. Am J Phys Med Rehabil. 2012 Sep;91(9):814-20. doi: 10.1097/PHM.0b013e31825f13a3.

  PMID: 22760104 BACKGROUND

• Theilig S, Podubecka J, Bosl K, Wiederer R, Nowak DA. Functional neuromuscular stimulation to improve severe hand dysfunction after stroke: does inhibitory rTMS enhance therapeutic efficiency? Exp Neurol. 2011 Jul;230(1):149-55. doi: 10.1016/j.expneurol.2011.04.010. Epub 2011 Apr 16.

  PMID: 21524650 BACKGROUND

• Wassermann EM, Wedegaertner FR, Ziemann U, George MS, Chen R. Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation. Neurosci Lett. 1998 Jul 10;250(3):141-4. doi: 10.1016/s0304-3940(98)00437-6.

  PMID: 9708852 BACKGROUND

• Weiduschat N, Thiel A, Rubi-Fessen I, Hartmann A, Kessler J, Merl P, Kracht L, Rommel T, Heiss WD. Effects of repetitive transcranial magnetic stimulation in aphasic stroke: a randomized controlled pilot study. Stroke. 2011 Feb;42(2):409-15. doi: 10.1161/STROKEAHA.110.597864. Epub 2010 Dec 16.

  PMID: 21164121 BACKGROUND

• Braddom, Randall L., Ralph M. Buschbacher. Ch 30 Spasticity Management. Physical Medicine & Rehabilitation. Saunders Elsevier 2007; 641-55.

  BACKGROUND

MeSH Terms

Conditions

Muscle Spasticity

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Kate Frost
• Organization: University of Minnesota

jahnke.k.131@gmail.com

612-626-4913

Study Officials

• Matthew J Timp, DO

  University of Minnesota, Physical Medicine and Rehabilitation

  PRINCIPAL INVESTIGATOR

• James R Carey, PhD, PT

  University of Minnesota, Program in Physical Therapy

  STUDY CHAIR

• Florence S John, MD, MPH

  University of Minnesota, Physical Medicine and Rehabilitation

  STUDY DIRECTOR

• Kate Frost, MS

  University of Minnesota, Program in Physical Therapy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: October 20, 2014
• Study Start: December 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2025-01

Locations

US (1)