Plasticity in the Spinal Cord to Enhance Motor Retraining After Stroke

Altered Connections in the Spinal Cord to Reduce Hand Impairment After Stroke

Sponsors

Lead sponsor: VA Office of Research and Development

Collaborator: University of Pittsburgh

Source VA Office of Research and Development
Brief Summary

The goals of this study are to leverage principles of spike timing-dependent plasticity (STDP) via non-invasive stimulation techniques to strengthen corticospinal transmission. Few studies have targeted the cortex after stroke in humans, and none have targeted the corticospinal-motoneuronal synapse in the spinal cord. This study, therefore, is a novel approach to studying neuroplasticity after stroke. Previous work in humans with incomplete spinal cord injury demonstrates that the resulting plasticity transiently enhances motor output, indicating that there is also therapeutic potential.

Detailed Description

Stroke is a leading cause of serious long-term disability in the United States with 795,000 individuals suffering a new or recurrent stroke each year. In most cases, disability is associated with incomplete motor recovery of the paretic limb. Even with intensive therapy, full recovery is often not achieved. Thus, there is a need for mechanistic approaches that drive the impaired neuronal targets of retraining to fully harness the corticospinal system's adaptive capacity.

This study will attempt to induce bi-directional STDP in corticospinal-motoneuronal synapses serving an intrinsic hand muscle of the hemiparetic limb. Control experiments will be completed to provide evidence of the neurophysiological mechanism(s) mediating the effect and to examine behavioral effects.

Individuals who are at least 6 months post first-ever subcortical stroke and have at least partial range of motion of the paretic index finger will be invited to participate.

Overall Status Recruiting
Start Date February 4, 2019
Completion Date October 31, 2023
Primary Completion Date October 31, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Corticospinal Transmission 12 months
Secondary Outcome
Measure Time Frame
Motor output 12 months
Enrollment 48
Condition
Intervention

Intervention type: Procedure

Intervention name: Stimulation

Description: This study is a novel approach to studying neuroplasticity after stroke. Previous work in humans with incomplete spinal cord injury demonstrates that the resulting plasticity transiently enhances motor output, indicating that there is also therapeutic potential. This study will attempt to induce bi-directional plasticity in corticospinal-motoneuronal synapses serving an intrinsic hand muscle of the hemiparetic limb. Control experiments will be completed to provide evidence of the neurophysiological mechanism(s) mediating the effect and to examine behavioral effects.

Eligibility

Criteria:

Inclusion Criteria:

- Between the ages of 18 and 75 years old

- Subjects must show an understanding of the study goals and have the ability to follow simple directions as judged by the investigators

- Diagnosis of first ever stroke

- Stroke onset of at least six months prior to the time of participation

- Some residual muscle activity in the first dorsal interosseous muscle (Score of 1 or greater on MRC Scale)

- Subjects must show an understanding of the study goals and have the ability to follow simple directions as judged by the investigators.

Exclusion Criteria:

- History of seizure or epilepsy

- Metallic implants in the head or neck

- Ferromagnetic metallic implants, pacemakers, other implanted devices, or ventilators (for subjects undergoing MRI)

- Pregnant or expecting to become pregnant

- Difficulty maintaining alertness and/or remaining still

- Body weight > 300 lbs due to MRI scanner dimensions (for subjects undergoing MRI)

- Hemispatial neglect, aphasia, or cognitive or language impairment that would impact testing and would interfere with the ability to follow simple instructions, as judged by the investigators

- Diagnosis of neurological disorder(s) other than stroke influence movement

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Michael A. Urbin, PhD Principal Investigator VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Overall Contact

Last name: Debbie E Harrington, BS

Phone: (412) 383-1355

Email: [email protected]

Location
facility status contact investigator VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA Debbie E Harrington, BS 412-383-1355 [email protected] Michael A. Urbin, PhD Principal Investigator
Location Countries

United States

Verification Date

February 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Stroke

Arm group type: Experimental

Description: This study will attempt to induce bi-directional plasticity in corticospinal-motoneurlonal synapses serving an intrinsic hand muscle of the hemiparetic limb using stimulation. Individuals who are at least 6 months post-ever subcortical stroke and have at least partial range of motion of the paretic index finger will be invited to participate.

Arm group label: Control

Arm group type: Placebo Comparator

Description: Control experiments will be completed to provide evidence of the neurophysiological mechanism(s) mediating the effect and to examine behavioral effects of stimulation. Individuals without a history of stroke will be recruited to participate.

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention model description: The purpose of the study is to induce plasticity in corticospinal-motoneuronal synapses serving an intrinsic hand muscle of the hemiparetic limb in humans with stroke. Neurologically-intact controls are included to verify that an effect was present in absence of stroke

Primary purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov