Efficacy of contralaterally controlled functional electrical stimulation compared to cyclic neuromuscular electrical stimulation and task-oriented training for recovery of hand function after stroke: study protocol for a multi-site randomized controlled trial

Jayme S Knutson, Amy S Friedl, Kristine M Hansen, Mary Y Harley, A M Barrett, Preeti Raghavan, Ela B Plow, Douglas D Gunzler, John Chae, Jayme S Knutson, Amy S Friedl, Kristine M Hansen, Mary Y Harley, A M Barrett, Preeti Raghavan, Ela B Plow, Douglas D Gunzler, John Chae

Abstract

Background: Multi-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites.

Methods: Up to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment.

Discussion: Loss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination.

Trial registration: ClinicalTrials.gov NCT03574623 . Registered prior to first enrollment; July 2, 2018.

Keywords: Electrical stimulation; Hemiparesis; Stroke rehabilitation; Therapy; Upper extremity.

Conflict of interest statement

JSK and JC are co-inventors on the CCFES patent assigned to Case Western Reserve University, Patent 8,165,685: System and Method for Therapeutic Neuromuscular Electrical Stimulation. This patent was licensed to Synapse Biomedical Inc., Oberlin, Ohio, on February 1, 2019.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Contralaterally controlled functional electrical stimulation (CCFES) enables stroke survivors to open their paretic hand. The stroke survivor controls the amount of hand opening through a CCFES glove worn on their unaffected hand, which controls the intensity of electrical stimulation delivered to the finger and thumb extensor muscles of the paretic hand. The CCFES system enables stroke survivors to practice using their paretic hand to perform tasks in therapy and to self-administer hand opening exercises. Illustration by Erika Woodrum, CMI. © 2021 Cleveland FES Center, Cleveland, OH

References

    1. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart Disease and Stroke Statistics-2021 Update: a report from the American Heart Association. Circulation. 2021;143(8):e254–e743.
    1. Lai SM, Studenski S, Duncan PW, Perera S. Persisting consequences of stroke measured by the Stroke Impact Scale. Stroke. 2002;33(7):1840–1844.
    1. Lang CE, DeJong SL, Beebe JA. Recovery of thumb and finger extension and its relation to grasp performance after stroke. J Neurophysiol. 2009;102(1):451–459.
    1. Kamper DG, Fischer HC, Cruz EG, Rymer WZ. Weakness is the primary contributor to finger impairment in chronic stroke. Arch Phys Med Rehabil. 2006;87(9):1262–1269.
    1. Franceschini M, La Porta F, Agosti M, Massucci M. group ICR. Is health-related-quality of life of stroke patients influenced by neurological impairments at one year after stroke? Eur J Phys Rehabil Med. 2010;46(3):389–399.
    1. Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996;272(5269):1791–1794.
    1. Johansson BB. Brain plasticity and stroke rehabilitation. Willis Lecture Stroke. 2000;31(1):223–230.
    1. Jenkins WM, Merzenich MM. Reorganization of neocortical representations after brain injury: a neurophysiological model of the bases of recovery from stroke. Prog Brain Res. 1987;71:249–266.
    1. Merzenich MM, Jenkins WM. Reorganization of cortical representations of the hand following alterations of skin inputs induced by nerve injury, skin island transfers, and experience. J Hand Ther. 1993;6(2):89–104.
    1. Merzenich MM, Kaas JH, Wall J, Nelson RJ, Sur M, Felleman D. Topographic reorganization of somatosensory cortical areas 3b and 1 in adult monkeys following restricted deafferentation. Neuroscience. 1983;8(1):33–55.
    1. Merzenich MM, Nelson RJ, Stryker MP, Cynader MS, Schoppmann A, Zook JM. Somatosensory cortical map changes following digit amputation in adult monkeys. J Comp Neurol. 1984;224(4):591–605.
    1. Kew JJ, Ridding MC, Rothwell JC, Passingham RE, Leigh PN, Sooriakumaran S, et al. Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation. J Neurophysiol. 1994;72(5):2517–2524.
    1. Mogilner A, Grossman JA, Ribary U, Joliot M, Volkmann J, Rapaport D, et al. Somatosensory cortical plasticity in adult humans revealed by magnetoencephalography. Proc Natl Acad Sci U S A. 1993;90(8):3593–3597.
    1. Pascual-Leone A, Torres F. Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers. Brain. 1993;116(Pt 1):39–52.
    1. Buonomano DV, Merzenich MM. Cortical plasticity: from synapses to maps. Annu Rev Neurosci. 1998;21:149–186.
    1. Malenka RC, Nicoll RA. Long-term potentiation--a decade of progress? Science. 1999;285(5435):1870–1874.
    1. Knutson JS, Harley MY, Hisel TZ, Chae J. Improving hand function in stroke survivors: a pilot study of contralaterally controlled functional electric stimulation in chronic hemiplegia. Arch Phys Med Rehabil. 2007;88(4):513–520.
    1. Knutson JS, Gunzler DD, Wilson RD, Chae J. Contralaterally controlled functional electrical stimulation improves hand dexterity in chronic hemiparesis: a randomized trial. Stroke. 2016;47:2696–2602.
    1. Knutson JS, Harley MY, Hisel TZ, Hogan SD, Maloney MM, Chae J. Contralaterally controlled functional electrical stimulation for upper extremity hemiplegia: an early-phase randomized clinical trial in subacute stroke patients. Neurorehabil Neural Repair. 2012;26(3):239–246.
    1. Knutson JS, Hisel TZ, Harley MY, Chae J. A novel functional electrical stimulation treatment for recovery of hand function in hemiplegia: 12-week pilot study. Neurorehabil Neural Repair. 2009;23(1):17–25.
    1. Knutson JS, Makowski NS, Harley MY, Hisel TZ, Gunzler DD, Wilson RD, et al. Adding contralaterally controlled electrical stimulation of the triceps to contralaterally controlled functional electrical stimulation of the finger extensors reduces upper limb impairment and improves reachable workspace but not dexterity: a randomized controlled trial. Am J Phys Med Rehabil. 2020;99(6):514–521.
    1. Zheng Y, Mao M, Cao Y, Lu X. Contralaterally controlled functional electrical stimulation improves wrist dorsiflexion and upper limb function in patients with early-phase stroke: A randomized controlled trial. J Rehabil Med. 2019;51(2):103–108.
    1. Shen Y, Yin Z, Fan Y, Chen CF, Dai W, Yi W, et al. Comparison of the effects of contralaterally controlled functional electrical stimulation and neuromuscular electrical stimulation on upper extremity functions in patients with stroke. CNS Neurol Disord Drug Targets. 2015;14(10):1260–1266.
    1. Nascimento LR, Michaelsen SM, Ada L, Polese JC, Teixeira-Salmela LF. Cyclical electrical stimulation increases strength and improves activity after stroke: a systematic review. J Physiother. 2014;60(1):22–30.
    1. Chae J, Bethoux F, Bohine T, Dobos L, Davis T, Friedl A. Neuromuscular stimulation for upper extremity motor and functional recovery in acute hemiplegia. Stroke. 1998;29(5):975–979.
    1. Hsu SS, Hu MH, Wang YH, Yip PK, Chiu JW, Hsieh CL. Dose-response relation between neuromuscular electrical stimulation and upper-extremity function in patients with stroke. Stroke. 2010;41(4):821–824.
    1. Knutson JS, Fu MJ, Sheffler LR, Chae J. Neuromuscular electrical stimulation for motor restoration in hemiplegia. Phys Med Rehabil Clin N Am. 2015;26(4):729–745.
    1. Harris JE, Eng JJ, Miller WC, Dawson AS. A self-administered Graded Repetitive Arm Supplementary Program (GRASP) improves arm function during inpatient stroke rehabilitation: a multi-site randomized controlled trial. Stroke. 2009;40(6):2123–2128.
    1. Organization WH . How to use the ICF: a practical manual for using the International Classification of Funcitoning, Disability and Health (ICF) Geneva: WHO: World Health Organization; 2013.
    1. Database RM . Rehabilitation Measures Database. Rehab Measures: Box and Block Test. 2016.
    1. Salter K, Campbell N, Richardson M, Mehta S, Jutai J, Zettler L, et al. Chapter 21. Outcome Measures in Stroke Rehabilitation. In: Teasell R, editor. Evidence-Based Review of Stroke Rehabilitation 16th Edition. London; 2013. .
    1. Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985;39(6):386–391.
    1. Desrosiers J, Bravo G, Hebert R, Dutil E, Mercier L. Validation of the Box and Block Test as a measure of dexterity of elderly people: reliability, validity, and norms studies. Arch Phys Med Rehabil. 1994;75(7):751–755.
    1. Chen HM, Chen CC, Hsueh IP, Huang SL, Hsieh CL. Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke. Neurorehabil Neural Repair. 2009;23(5):435–440.
    1. Ghaziani E, Couppe C, Henkel C, Siersma V, Sondergaard M, Christensen H, et al. Electrical somatosensory stimulation followed by motor training of the paretic upper limb in acute stroke: study protocol for a randomized controlled trial. Trials. 2017;18(1):84.
    1. Page SJ, Fulk GD, Boyne P. Clinically important differences for the upper-extremity Fugl-Meyer Scale in people with minimal to moderate impairment due to chronic stroke. Phys Ther. 2012;92(6):791–798.
    1. Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13–31.
    1. Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther. 1983;63(10):1606–10.
    1. Roorda LD, Houwink A, Smits W, Molenaar IW, Geurts AC. Measuring upper limb capacity in poststroke patients: development, fit of the monotone homogeneity model, unidimensionality, fit of the double monotonicity model, differential item functioning, internal consistency, and feasibility of the stroke upper limb capacity scale. SULCS Arch Phys Med Rehabil. 2011;92(2):214–227.
    1. Houwink A, Roorda LD, Smits W, Molenaar IW, Geurts AC. Measuring upper limb capacity in patients after stroke: reliability and validity of the stroke upper limb capacity scale. Arch Phys Med Rehabil. 2011;92(9):1418–1422.
    1. Knutson JS, Friedl AS, Hansen KM, Hisel TZ, Harley MY. Convergent validity and responsiveness of the SULCS. Arch Phys Med Rehabil. 2019;100(1):140–3 e1.
    1. Platz T, Pinkowski C, van Wijck F, Kim IH, di Bella P, Johnson G. Reliability and validity of arm function assessment with standardized guidelines for the Fugl-Meyer Test, Action Research Arm Test and Box and Block Test: a multicentre study. Clin Rehabil. 2005;19(4):404–411.
    1. Yozbatiran N, Der-Yeghiaian L, Cramer SC. A standardized approach to performing the action research arm test. Neurorehabil Neural Repair. 2008;22(1):78–90.
    1. Hsieh CL, Hsueh IP, Chiang FM, Lin PH. Inter-rater reliability and validity of the action research arm test in stroke patients. Age Ageing. 1998;27(2):107–113.
    1. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67(2):206–207.
    1. Duncan PW, Bode RK, Min Lai S, Perera S. Glycine antagonist in neuroprotection Americans I. Rasch analysis of a new stroke-specific outcome scale: the Stroke Impact Scale. Arch Phys Med Rehabil. 2003;84(7):950–963.
    1. Cella D, Lai JS, Nowinski CJ, Victorson D, Peterman A, Miller D, et al. Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology. Neurology. 2012;78(23):1860–1867.
    1. Cunningham DA, Machado A, Janini D, Varnerin N, Bonnett C, Yue G, et al. Assessment of inter-hemispheric imbalance using imaging and noninvasive brain stimulation in patients with chronic stroke. Arch Phys Med Rehabil. 2015;96(4 Suppl):S94–103.
    1. Tazoe T, Perez MA. Selective activation of ipsilateral motor pathways in intact humans. J Neurosci. 2014;34(42):13924–13934.
    1. Perez MA, Cohen LG. Scaling of motor cortical excitability during unimanual force generation. Cortex. 2009;45(9):1065–1071.
    1. Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther. 1974;15(5):443–453.
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31(1):103–115.
    1. Wolf SL, Winstein CJ, Miller JP, Taub E, Uswatte G, Morris D, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. Jama. 2006;296(17):2095–2104.
    1. Connell LA, McMahon NE, Harris JE, Watkins CL, Eng JJ. A formative evaluation of the implementation of an upper limb stroke rehabilitation intervention in clinical practice: a qualitative interview study. Implement Sci. 2014;9:90.
    1. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381.
    1. Fitzmaurice GM, Laird NM, Ware JH. Applied longitudinal analysis. New York: Wiley; 2012.
    1. Baron RM, Kenny DA. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986;51(6):1173–1182.
    1. Cunningham DA, Knutson JS, Sankarasubramanian V, Potter-Baker KA, Machado AG, Plow EB. Bilateral contralaterally controlled functional electrical stimulation reveals new insights into the interhemispheric competition model in chronic stroke. Neurorehabil Neural Repair. 2019;33(9):707–717.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever