Clinical trial NCT06404268: Facilitating Neuroplastic Changes of Acute Stroke Survivors
Official title: Facilitating Neuroplastic Changes of Acute Stroke Survivors With Severe Hemiplegia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Stroke
Keywords: Stroke
Paraplegia
Acute
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: The University of Texas Health Science Center, Houston
First posted: 2024-05-08
Enrollment: 68
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized clinical trial with the study group and control group
Primary purpose: TREATMENT

Brief summary: This project will develop a wearable rehabilitation robot suitable for in-bed acute stage rehabilitation. It involves robot-guided motor relearning, passive and active motor-sensory rehabilitation early in the acute stage post-stroke including patients who are paralyzed with no motor output. The early acute stroke rehabilitation device will be evaluated in this clinical trial.

Detailed description: Stroke survivors often experience loss of motor control and impaired function. Immediately after stroke, there is a time-limited window of heightened plasticity during which the greatest gains in recovery occur. Therefore, early intensive sensorimotor rehabilitation post-stroke is critical in improving functional outcomes and minimizing disability. However, acute stroke survivors often receive little active training to improve mobility during their hospital stay and they are left alone during most of the day. Especially for those acute patients with no voluntary motor output, active motor training might be even less, partly due to a lack of rehabilitation protocols to detect potential motor recovering signals sensitively and facilitate neuroplastic changes. To address this unmet clinical need, this project will develop a novel wearable rehabilitation robot suitable for in-bed acute stage rehabilitation with guided motor relearning, passive and active motor-sensory rehabilitation early in the acute stage post-stroke including patients who are paralyzed with no motor output. The early acute stroke rehabilitation device will be evaluated in this clinical trial.

Eligibility criteria: Inclusion Criteria:

* Acute first time unilateral hemispheric stroke (hemorrhagic or ischemic stroke, 24 hours after admission to 1 month post-stroke at the start of the proposed treatment)
* Hemiplegia or hemiparesis
* 0≤Manual Muscle Testing (MMT)\<=2
* Age 30-85
* Ankle impairments including stiff calf muscles and/or inadequate dorsiflexion

Exclusion Criteria:

* Medically not stable
* Associated acute medical illness that interferes with ability to training and exercise
* No impairment or very mild ankle impairment of ankle
* Severe cardiovascular problems that interfere with ability to perform moderate movement exercises
* Cognitive impairment or aphasia with inability to follow instructions
* Severe pain in legs
* Severe ankle contracture greater than 15° plantar flexion (when pushing ankle to dorsiflexion)
* Pressure ulcer, recent surgical incision or active skin disease with open wounds present below knee

Primary outcomes:
measure: Fugl-Meyer Lower Extremity (FMLE)
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends]
Secondary outcomes:
measure: Active range of motion (AROM)
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends
measure: Passive Range of Motion (PROM) will be measured in degrees in the ankle joint while the robot moves the ankle of the subject strongly.
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends
measure: Strength of the ankle flexor-extensor muscle will be measured in Newtons
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends
measure: Modified Ashworth Scale (MAS)
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends
measure: Berg Balance Scale
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends
measure: 10-meter Walk Test
timeFrame: At the beginning and end of 3-week training, and 1 month after the treatment ends
Other outcomes:
Locations:
Study officials:
affiliation: University of Maryland
name: Li-Qun Zhang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang C, Huang MZ, Kehs GJ, Braun RG, Cole JW, Zhang LQ. Intensive In-Bed Sensorimotor Rehabilitation of Early Subacute Stroke Survivors With Severe Hemiplegia Using a Wearable Robot. IEEE Trans Neural Syst Rehabil Eng. 2021;29:2252-2259. doi: 10.1109/TNSRE.2021.3121204. Epub 2021 Nov 4.
citation: Krakauer JW, Carmichael ST, Corbett D, Wittenberg GF. Getting neurorehabilitation right: what can be learned from animal models? Neurorehabil Neural Repair. 2012 Oct;26(8):923-31. doi: 10.1177/1545968312440745. Epub 2012 Mar 30.
citation: Langhorne P, Bernhardt J, Kwakkel G. Stroke rehabilitation. Lancet. 2011 May 14;377(9778):1693-702. doi: 10.1016/S0140-6736(11)60325-5.
citation: Nudo RJ, Milliken GW. Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. J Neurophysiol. 1996 May;75(5):2144-9. doi: 10.1152/jn.1996.75.5.2144.
citation: Ren Y, Wu YN, Yang CY, Xu T, Harvey RL, Zhang LQ. Developing a Wearable Ankle Rehabilitation Robotic Device for in-Bed Acute Stroke Rehabilitation. IEEE Trans Neural Syst Rehabil Eng. 2017 Jun;25(6):589-596. doi: 10.1109/TNSRE.2016.2584003. Epub 2016 Jun 22.
citation: Sanger TD, Delgado MR, Gaebler-Spira D, Hallett M, Mink JW; Task Force on Childhood Motor Disorders. Classification and definition of disorders causing hypertonia in childhood. Pediatrics. 2003 Jan;111(1):e89-97. doi: 10.1542/peds.111.1.e89.
citation: Selles RW, Li X, Lin F, Chung SG, Roth EJ, Zhang LQ. Feedback-controlled and programmed stretching of the ankle plantarflexors and dorsiflexors in stroke: effects of a 4-week intervention program. Arch Phys Med Rehabil. 2005 Dec;86(12):2330-6. doi: 10.1016/j.apmr.2005.07.305.
citation: Sukal-Moulton T, Clancy T, Zhang LQ, Gaebler-Spira D. Clinical application of a robotic ankle training program for cerebral palsy compared to the research laboratory application: does it translate to practice? Arch Phys Med Rehabil. 2014 Aug;95(8):1433-40. doi: 10.1016/j.apmr.2014.04.010. Epub 2014 May 2.
citation: Waldman G, Yang CY, Ren Y, Liu L, Guo X, Harvey RL, Roth EJ, Zhang LQ. Effects of robot-guided passive stretching and active movement training of ankle and mobility impairments in stroke. NeuroRehabilitation. 2013;32(3):625-34. doi: 10.3233/NRE-130885.
citation: Wu YN, Hwang M, Ren Y, Gaebler-Spira D, Zhang LQ. Combined passive stretching and active movement rehabilitation of lower-limb impairments in children with cerebral palsy using a portable robot. Neurorehabil Neural Repair. 2011 May;25(4):378-85. doi: 10.1177/1545968310388666. Epub 2011 Feb 22.
citation: Wu YN, Ren Y, Goldsmith A, Gaebler D, Liu SQ, Zhang LQ. Characterization of spasticity in cerebral palsy: dependence of catch angle on velocity. Dev Med Child Neurol. 2010 Jun;52(6):563-9. doi: 10.1111/j.1469-8749.2009.03602.x. Epub 2010 Jan 28.
citation: Xerri C, Merzenich MM, Peterson BE, Jenkins W. Plasticity of primary somatosensory cortex paralleling sensorimotor skill recovery from stroke in adult monkeys. J Neurophysiol. 1998 Apr;79(4):2119-48. doi: 10.1152/jn.1998.79.4.2119.
citation: Yang CY, Guo X, Ren Y, Kang SH, Zhang LQ. Position-dependent, hyperexcitable patellar reflex dynamics in chronic stroke. Arch Phys Med Rehabil. 2013 Feb;94(2):391-400. doi: 10.1016/j.apmr.2012.09.029. Epub 2012 Oct 11.
citation: Zhang LQ, Chung SG, Ren Y, Liu L, Roth EJ, Rymer WZ. Simultaneous characterizations of reflex and nonreflex dynamic and static changes in spastic hemiparesis. J Neurophysiol. 2013 Jul;110(2):418-30. doi: 10.1152/jn.00573.2012. Epub 2013 May 1.
citation: Zhang LQ, Rymer WZ. Reflex and intrinsic changes induced by fatigue of human elbow extensor muscles. J Neurophysiol. 2001 Sep;86(3):1086-94. doi: 10.1152/jn.2001.86.3.1086.
citation: Zhang LQ, Wang G, Nishida T, Xu D, Sliwa JA, Rymer WZ. Hyperactive tendon reflexes in spastic multiple sclerosis: measures and mechanisms of action. Arch Phys Med Rehabil. 2000 Jul;81(7):901-9. doi: 10.1053/apmr.2000.5582.
citation: Zhao H, Wu YN, Hwang M, Ren Y, Gao F, Gaebler-Spira D, Zhang LQ. Changes of calf muscle-tendon biomechanical properties induced by passive-stretching and active-movement training in children with cerebral palsy. J Appl Physiol (1985). 2011 Aug;111(2):435-42. doi: 10.1152/japplphysiol.01361.2010. Epub 2011 May 19.
citation: Albert SJ, Kesselring J. Neurorehabilitation of stroke. J Neurol. 2012 May;259(5):817-32. doi: 10.1007/s00415-011-6247-y. Epub 2011 Oct 1.
citation: Bernhardt J, Chan J, Nicola I, Collier JM. Little therapy, little physical activity: rehabilitation within the first 14 days of organized stroke unit care. J Rehabil Med. 2007 Jan;39(1):43-8. doi: 10.2340/16501977-0013.
citation: Bernhardt J, Dewey H, Thrift A, Donnan G. Inactive and alone: physical activity within the first 14 days of acute stroke unit care. Stroke. 2004 Apr;35(4):1005-9. doi: 10.1161/01.STR.0000120727.40792.40. Epub 2004 Feb 26.
citation: Chung SG, van Rey E, Bai Z, Rymer WZ, Roth EJ, Zhang LQ. Separate quantification of reflex and nonreflex components of spastic hypertonia in chronic hemiparesis. Arch Phys Med Rehabil. 2008 Apr;89(4):700-10. doi: 10.1016/j.apmr.2007.09.051.
citation: Chung SG, Van Rey E, Bai Z, Roth EJ, Zhang LQ. Biomechanic changes in passive properties of hemiplegic ankles with spastic hypertonia. Arch Phys Med Rehabil. 2004 Oct;85(10):1638-46. doi: 10.1016/j.apmr.2003.11.041.
citation: Chen K, Wu YN, Ren Y, Liu L, Gaebler-Spira D, Tankard K, Lee J, Song W, Wang M, Zhang LQ. Home-Based Versus Laboratory-Based Robotic Ankle Training for Children With Cerebral Palsy: A Pilot Randomized Comparative Trial. Arch Phys Med Rehabil. 2016 Aug;97(8):1237-43. doi: 10.1016/j.apmr.2016.01.029. Epub 2016 Feb 20.
citation: Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society; Delgado MR, Hirtz D, Aisen M, Ashwal S, Fehlings DL, McLaughlin J, Morrison LA, Shrader MW, Tilton A, Vargus-Adams J. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2010 Jan 26;74(4):336-43. doi: 10.1212/WNL.0b013e3181cbcd2f.
citation: Gao F, Grant TH, Roth EJ, Zhang LQ. Changes in passive mechanical properties of the gastrocnemius muscle at the muscle fascicle and joint levels in stroke survivors. Arch Phys Med Rehabil. 2009 May;90(5):819-26. doi: 10.1016/j.apmr.2008.11.004.
citation: Gao F, Ren Y, Roth EJ, Harvey R, Zhang LQ. Effects of repeated ankle stretching on calf muscle-tendon and ankle biomechanical properties in stroke survivors. Clin Biomech (Bristol). 2011 Jun;26(5):516-22. doi: 10.1016/j.clinbiomech.2010.12.003. Epub 2011 Jan 6.
citation: Gao F, Zhang LQ. Altered contractile properties of the gastrocnemius muscle poststroke. J Appl Physiol (1985). 2008 Dec;105(6):1802-8. doi: 10.1152/japplphysiol.90930.2008. Epub 2008 Oct 23.
citation: 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;71:249-66. doi: 10.1016/s0079-6123(08)61829-4. No abstract available.