Transspinal-Transcortical Paired Stimulation for Neuroplasticity and Recovery After SCI

NCT04624607 | Completed FDA Device

• 2 other identifiers: 2017-0261C32095GG
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

People with spinal cord injury (SCI) have motor dysfunction that results in substantial social, personal, and economic costs. Uncontrolled muscle spasticity and motor dysfunction result in disabilities that significantly reduce quality of life. Several rehabilitation interventions are utilized to treat muscle spasticity and motor dysfunction after SCI in humans. However, because most interventions rely on sensory afferent feedback that is interpreted by malfunctioned neuronal networks, rehabilitation efforts are greatly compromised. On the other hand, changes in the function of nerve cells connecting the brain and spinal cord have been reported following repetitive electromagnetic stimulation delivered over the head and legs or arms at specific time intervals. In addition, evidence suggests that electrical signals delivered to the spinal cord can regenerate spinal motor neurons in injured animals. A fundamental knowledge gap still exists on neuroplasticity and recovery of leg motor function in people with SCI after repetitive transspinal cord and transcortical stimulation. In this project, it is proposed that repetitive pairing of transspinal cord stimulation with transcortical stimulation strengthens the connections between the brain and spinal cord, decreases ankle spasticity, and improves leg movement. People with motor incomplete SCI will receive transspinal - transcortical paired associative stimulation at rest and during assisted stepping. The effects of this novel neuromodulation paradigm will be established via clinical tests and noninvasive neurophysiological methods that assess the pathways connecting the brain with the spinal cord.

Conditions

Spinal Cord Injuries; Paraplegia, Spinal; Tetraplegia/Tetraparesis

Keywords

Spinal Cord Injury; Locomotor Training; Neuromodulation; Paired-Associative Stimulation

Outcome Measures

Primary Outcomes (2)

• Plasticity of cortical and corticospinal neural circuits

  Neurophysiological tests probing cortical and corticospinal excitability will be measured before and after the intervention. Single-pulse transcranial magnetic stimulation (TMS) will be used to assemble the recruitment curve of motor evoked potentials, and paired-pulse TMS will be used to probe changes in cortical inhibitory and facilitatory neuronal circuits.

  3 years

• Plasticity of spinal neural cicuits

  Neurophysiological tests probing spinal reflex excitability will be measured before and after each intervention by posterior tibial and sural nerves stimulation during Lokomat-assisted stepping depicting the amplitude modulation of the soleus H-reflex, tibialis anterior flexor reflex, and interlimb reflexes.

  3 years

Secondary Outcomes (2)

• Sensorimotor leg motor function

  3 years

• Walking function

  3 years

Study Arms (2)

Transspinal-transcortical paired-associative stimiulation combined with robotic gait training

EXPERIMENTAL

Robotic gait training will be administered along with paired non-invasive transspinal stimulation over the thoracolumbar region and non-invasive brain stimulation during assisted stepping.

Device: Transspinal-transcortical paired-associative stimiulation combined with robotic gait training

Transcortical-transspinal paired-associative stimiulation combined with robotic gait training

EXPERIMENTAL

Robotic gait training will be administered along with paired non-invasive brain stimulation and non-invasive transspinal stimulation over the thoracolumbar region during assisted stepping.

Device: Transcortical-transspinal paired-associative stimiulation combined with robotic gait training

Interventions

Transspinal-transcortical paired-associative stimiulation combined with robotic gait training DEVICE

Individuals with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also paired non-invasive transspinal stimulation and non-invasive brain stimulation during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Transspinal-transcortical paired-associative stimiulation combined with robotic gait training

Transcortical-transspinal paired-associative stimiulation combined with robotic gait training DEVICE

Individuals with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also paired non-invasive brain stimulation and non-invasive transspinal stimulation during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Transcortical-transspinal paired-associative stimiulation combined with robotic gait training

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of motor incomplete spinal cord injury (SCI).
• SCI is above thoracic 12 vertebra.
• Absent permanent ankle joint contractures.
• SCI occurred 6 months before enrollment to the study.

You may not qualify if:

• Supraspinal lesions
• Neuropathies of the peripheral nervous system
• Degenerative neurological disorders
• Presence of pressure sores
• Urinary tract infection
• Neoplastic or vascular disorders of the spine or spinal cord
• Pregnant women or women who suspect they may be or may become pregnant
• People with cochlear implants, pacemaker, and implanted simulators
• People with history of seizures
• People with implanted Baclofen pump

Sponsors & Collaborators

• College of Staten Island, the City University of New York: lead

Study Sites (1)

Department of Physical Therapy, College of Staten Island, City University of New York

Staten Island, New York, 10314, United States

Location

Related Publications (11)

• Dixon L, Ibrahim MM, Santora D, Knikou M. Paired associative transspinal and transcortical stimulation produces plasticity in human cortical and spinal neuronal circuits. J Neurophysiol. 2016 Aug 1;116(2):904-16. doi: 10.1152/jn.00259.2016. Epub 2016 Jun 8.

  PMID: 27281748 BACKGROUND

• Knikou M. Spinal Excitability Changes after Transspinal and Transcortical Paired Associative Stimulation in Humans. Neural Plast. 2017;2017:6751810. doi: 10.1155/2017/6751810. Epub 2017 Oct 16.

  PMID: 29123926 BACKGROUND

• Knikou M. Functional reorganization of soleus H-reflex modulation during stepping after robotic-assisted step training in people with complete and incomplete spinal cord injury. Exp Brain Res. 2013 Jul;228(3):279-96. doi: 10.1007/s00221-013-3560-y. Epub 2013 May 25.

  PMID: 23708757 BACKGROUND

• Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain. 2000 Mar;123 Pt 3:572-84. doi: 10.1093/brain/123.3.572.

  PMID: 10686179 BACKGROUND

• Smith AC, Mummidisetty CK, Rymer WZ, Knikou M. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury. J Neurophysiol. 2014 Nov 1;112(9):2164-75. doi: 10.1152/jn.00308.2014. Epub 2014 Aug 13.

  PMID: 25122715 BACKGROUND

• Field-Fote EC, Roach KE. Influence of a locomotor training approach on walking speed and distance in people with chronic spinal cord injury: a randomized clinical trial. Phys Ther. 2011 Jan;91(1):48-60. doi: 10.2522/ptj.20090359. Epub 2010 Nov 4.

  PMID: 21051593 BACKGROUND

• Smith AC, Rymer WZ, Knikou M. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury. Exp Brain Res. 2015 Jan;233(1):89-103. doi: 10.1007/s00221-014-4094-7. Epub 2014 Sep 10.

  PMID: 25205562 BACKGROUND

• Taylor JL, Martin PG. Voluntary motor output is altered by spike-timing-dependent changes in the human corticospinal pathway. J Neurosci. 2009 Sep 16;29(37):11708-16. doi: 10.1523/JNEUROSCI.2217-09.2009.

  PMID: 19759317 BACKGROUND

• Song S, Miller KD, Abbott LF. Competitive Hebbian learning through spike-timing-dependent synaptic plasticity. Nat Neurosci. 2000 Sep;3(9):919-26. doi: 10.1038/78829.

  PMID: 10966623 BACKGROUND

• Thomas SL, Gorassini MA. Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. J Neurophysiol. 2005 Oct;94(4):2844-55. doi: 10.1152/jn.00532.2005. Epub 2005 Jul 6.

  PMID: 16000519 BACKGROUND

• Pulverenti TS, Zaaya M, Knikou M. Brain and spinal cord paired stimulation coupled with locomotor training affects polysynaptic flexion reflex circuits in human spinal cord injury. Exp Brain Res. 2022 Jun;240(6):1687-1699. doi: 10.1007/s00221-022-06375-x. Epub 2022 May 6.

  PMID: 35513720 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Paraplegia; Quadriplegia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Maria Knikou, PT, PhD

  College of Staten Island, City University of New York

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Individuals with Spinal Cord Injury will be assigned to receive robotic gait training with the Lokomat combined with paired non-invasive thoracolumbar transspinal stimulation and non-invasive brain stimulation.

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 12, 2020
• Study Start: January 5, 2018
• Primary Completion: February 10, 2020
• Study Completion: March 3, 2020
• Last Updated: November 13, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)