Spinal Cord Stimulation for Restoration of Arm and Hand Function in People With Subcortical Stroke

The goal of this study is to verify whether electrical stimulation of the cervical spinal cord can activate muscles of the arm and hand in people with hemiplegia following stroke. Participants will undergo a surgical procedure to implant a system which provides epidural electrical stimulation (EES) of the cervical spinal cord. Researchers will quantify the ability of EES to recruit arm and hand muscles and produce distinct kinematic movements. The implant will be removed after less than 30 days. Results of this study will provide the foundation for future studies evaluating the efficacy of a minimally-invasive neuro-technology that can be used in clinical neurorehabilitation programs to restore upper limb motor function in people with subcortical strokes, thereby increasing independence and quality of life.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cardiovascular Diseases; Stroke; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases
• Intervention / Treatment: Device: Epidural electrical stimulation (EES) of the cervical spinal cord

Detailed Description

Specifically, researchers will 1) quantify the motor potentials in arm and hand muscles generated by single pulses of electrical stimulation of the spinal cord using FDA-cleared devices 2) characterize optimal stimulation parameter ranges to maximize induced arm and hand movement, 3) measure neural changes that could be induced by the system, 4) characterize potential clinical effects by assessing patient mobility, spasticity, and neurophysiology with standard clinical tests and simple motor tasks.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy Boos, MS; Phone Number: 412-648-4179; Email: amy.boos@pitt.edu
• Study Contact Backup: Name: Lee Fisher, PhD; Phone Number: 412-383-1329; Email: lef44@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Single, ischemic or hemorrhagic stroke resulting in upper extremity hemiparesis more than 6 months prior to the time of enrollment. (Prior strokes that did not cause upper extremity motor deficits are not exclusionary.)
2. Participants must be between the ages of 21 and 70 years old.
3. Scores higher than 7 and lower than 50 on the Fugl-Meyer scale

Exclusion Criteria:

1. Serious disease or disorder (ex. neurological condition other than stroke, cancer, severe cardiac or respiratory disease, renal failure, etc.) or cognitive impairments that could affect the ability to participate in study activities.
2. Pregnancy or breast feeding.
3. Receiving anticoagulant, anti-spasticity or anti-epileptic medications throughout the duration of the study.
4. Presence of any implanted medical devices.
5. Severe claustrophobia.
6. Presence of joint contractures deemed by study clinician/investigator to be too severe to participate in study activities
7. Results from the Brief Symptoms Inventory (BSI-18) and additional discussions with the Principal Investigator and a study physician that deem participant inappropriate for the study.
8. Evaluation to sign consent form score <12.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Epidural electrical stimulation of the cervical spinal cord; Individuals with prior subcortical stroke and hemiparesis of the upper extremity.

Device: Epidural electrical stimulation (EES) of the cervical spinal cord; All participants enrolled in this group will undergo a surgical procedure to implant a system which provides epidural electrical stimulation (EES) of the cervical spinal cord. Researchers will quantify the ability of EES to recruit arm and hand muscles and produce distinct kinematic movements. The implant will be removed after less than 30 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Study is considered successful if no serious adverse events related to the use of electrical stimulation are reported	29 days
Discomfort and Pain	We will assess the relative level of discomfort and/or pain that is associated to the delivery of stimulation to the spinal cord. After each stimulation trains patients will be asked to report their perceived discomfort level using a 10 value subjective scale. Low values will be assigned to low discomfort, and high values to high discomfort.The study is considered successful if 70% of recruited subjects does not report discomfort or pain at stimulation amplitudes that are required to obtain motor responses in the muscles of the arm and hand	7, 14, 21, 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Impairment	The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. It is applied clinically and in research to determine disease severity, describe motor recovery, and to plan and assess treatment. The upper extremity motor function score ranges from 0 to 66 points. Minimal Detectable Change (MDC) is 5.2 points. The MCID (Minimally Clinically Important Difference) is 4.25 to 7.25.	15, 29 days
Dexterity / Function: Action Research Arm Test	The investigators will use the Action Research Arm Test (ARAT) assessment to quantify functional hand and arm dexterity. Performances will be compared with SCS-on against SCS-off. The investigators will consider as a minimally acceptable improvement an increase in the affected arm total score of >4 points. Comparison will be done per patient between Stim-on, Stim-off and pre-study baselines. Maximum score on the test is 57 points, minimum score is zero points, with a higher value indicating better dexterity/function.	7, 29 days
Single Joint Force	Isometric torque: measure the isometric torque produced by the subject at the shoulder, elbow and wrist joints. Comparison of SCS-on with SCS-off performance. Success Criteria: ≥20% increased torque production over SCS-off baseline as measured during single-joint isometric torque.	7, 14, 21, 29 days
Joint Velocity	The investigators will use the KINARM robot to quantify joint velocity. The investigators will measure 2D kinematics of the arm during several different horizontal reaching tasks. The investigators will also quantify joint velocity in 3D while subjects perform reach and grasp tasks unsupported. Subjects will be tasked to reach to targets or objects and manipulate objects while 3D videos of their arm and hand movements are recorded. Arm and hand kinematics will then be analyzed offline in parallel to EMG analysis of arm and hand muscles. Comparison will be done per patient between Stim-on and Stim-off at different time-points. Given the scientific nature of this task no minimal acceptable improvement is defined and data will be used to understand effects of SCS on arm kinematics.	7, 14, 21, 29 days
Movement Smoothness	The investigators will use the KINARM robot to quantify movement smoothness. The investigators will measure 2D kinematics of the arm during several different horizontal reaching tasks. The investigators will also quantify movement smoothness in 3D while subjects perform reach and grasp tasks unsupported. Subjects will be tasked to reach to targets or objects and manipulate objects while 3D videos of their arm and hand movements are recorded. Arm and hand kinematics will then be analyzed offline in parallel to EMG analysis of arm and hand muscles. Comparison will be done per patient between Stim-on and Stim-off at different time-points. Given the scientific nature of this task no minimal acceptable improvement is defined and data will be used to understand effects of SCS on arm kinematics.	7, 14, 21, 29 days
Time to Target	The investigators will use the KINARM robot to quantify time to target. The investigators will measure 2D kinematics of the arm during several different horizontal reaching tasks. The investigators will also quantify time to target in 3D while subjects perform reach and grasp tasks unsupported. Subjects will be tasked to reach to targets or objects and manipulate objects while 3D videos of their arm and hand movements are recorded. Arm and hand kinematics will then be analyzed offline in parallel to EMG analysis of arm and hand muscles. Comparison will be done per patient between Stim-on and Stim-off at different time-points. Given the scientific nature of this task no minimal acceptable improvement is defined and data will be used to understand effects of SCS on arm kinematics.	7, 14, 21, 29 days
Sensory motor integration: success-rate	The investigators will use the KINARM robot to quantify functional sensory acuity and sensory-motor integration. The investigators will measure 2D kinematics of the arm during different exercises where subjects will reach to defined targets with and without visual feedback. These tasks are designed to assess proprioception acuity and sensory-motor integration. Success-rate will be quantified offline. Comparison will be done per patient between Stim-on and Stim-off at different timepoints. Given the scientific nature of this task no minimal acceptable improvement is defined and data will be used to understand effects of SCS on sensorimotor integration processes.	7, 14, 21, 29 days
Sensory motor integration: displacement error	The investigators will use the KINARM robot to quantify functional sensory acuity and sensory-motor integration. The investigators will measure 2D kinematics of the arm during different exercises where subjects will reach to defined targets with and without visual feedback. These tasks are designed to assess proprioception acuity and sensory-motor integration. Displacement error from true target location will be quantified offline. Comparison will be done per patient between Stim-on and Stim-off at different timepoints. Given the scientific nature of this task no minimal acceptable improvement is defined and data will be used to understand effects of SCS on sensorimotor integration processes.	7, 14, 21, 29 days
Spasticity	The investigators will quantify spasticity scores using the Modified Ashworth Scale (MAS) for the shoulder, elbow and wrist joint and compare values with SCS-on and SCS-off. The investigators will consider as a minimally acceptable improvement a decrease of MAS >1, if available for the specific joint. Comparison will be done per patient between Stim-on and Stim-off and pre-study baselines. Maximum score on the MAS is 4, minimum score is 0, with a lower number indicating less spasticity.	7, 15, 21, 29 days
Sensorimotor Network Function	The investigators will perform resting state and motor-task functional MRI of the brain and spinal cord to quantify neural network activation at rest and during the execution of simple motor tasks.	29 days
Sensorimotor Network Structure Integrity	The investigators will perform High-definition Diffusion Weighted Imaging to quantify Fractional Anisotropy as a measurement of axon integrity in the brain and spinal cord pre and post study.	29 days
Cortico-spinal Tract Integrity	The investigators will measure muscle evoked potential consequent to Transcranial Magnetic Stimulation of the cortico-spinal tract to assess integrity of the cortico-spinal tract. They will also explore SCS responses when conditioned by a TMS pulse and vice-versa.	29 days
Spinal Circuit Excitability	The investigators will measure H-reflexes of arm muscles obtained during stimulation of the peripheral nerves to quantify excitability of spinal motoneurons to stimulation of primary sensory afferents pre and post-study. Expected Result: The main scientific hypothesis is that SCS will change sensori-to-motoneuron excitability that can be measured via H-reflex responses pre and post-implant.	7, days
Motoneuron Firing Rates	The investigators will use high-density EMGs on arm muscles to calculate firing rates of single spinal motoneuron discharge during isometric maximal voluntary contractions.	7, 14, 21, 29 days

Collaborators and Investigators

• Sponsor: Lee Fisher, PhD
• Investigators: Principal Investigator: Lee Fisher, PhD, University of Pittsburgh

Publications and helpful links

General Publications

• Capogrosso M, Milekovic T, Borton D, Wagner F, Moraud EM, Mignardot JB, Buse N, Gandar J, Barraud Q, Xing D, Rey E, Duis S, Jianzhong Y, Ko WK, Li Q, Detemple P, Denison T, Micera S, Bezard E, Bloch J, Courtine G. A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature. 2016 Nov 10;539(7628):284-288. doi: 10.1038/nature20118.
• Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 May;137(Pt 5):1394-409. doi: 10.1093/brain/awu038. Epub 2014 Apr 8. Erratum In: Brain. 2015 Feb;138(Pt 2):e330.
• Coscia M, Wessel MJ, Chaudary U, Millan JDR, Micera S, Guggisberg A, Vuadens P, Donoghue J, Birbaumer N, Hummel FC. Neurotechnology-aided interventions for upper limb motor rehabilitation in severe chronic stroke. Brain. 2019 Aug 1;142(8):2182-2197. doi: 10.1093/brain/awz181.
• Capogrosso M, Wenger N, Raspopovic S, Musienko P, Beauparlant J, Bassi Luciani L, Courtine G, Micera S. A computational model for epidural electrical stimulation of spinal sensorimotor circuits. J Neurosci. 2013 Dec 4;33(49):19326-40. doi: 10.1523/JNEUROSCI.1688-13.2013.
• Lu DC, Edgerton VR, Modaber M, AuYong N, Morikawa E, Zdunowski S, Sarino ME, Sarrafzadeh M, Nuwer MR, Roy RR, Gerasimenko Y. Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients. Neurorehabil Neural Repair. 2016 Nov;30(10):951-962. doi: 10.1177/1545968316644344. Epub 2016 May 18.
• Barra B, Roux C, Kaeser M, Schiavone G, Lacour SP, Bloch J, Courtine G, Rouiller EM, Schmidlin E, Capogrosso M. Selective Recruitment of Arm Motoneurons in Nonhuman Primates Using Epidural Electrical Stimulation of the Cervical Spinal Cord. Annu Int Conf IEEE Eng Med Biol Soc. 2018 Jul;2018:1424-1427. doi: 10.1109/EMBC.2018.8512554.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cerebrovascular Disorders; Stroke; Cardiovascular Diseases; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases
• Other Study ID Numbers: STUDY19090210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data may be shared with other researchers for the purpose of data analysis and collaboration.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No