Physiological Changes Induced Through MEP Conditioning in People With SCI

Characterization of Physiological Changes Induced Through Motor-evoked Potential Conditioning in People With Spinal Cord Injury

The study team is currently recruiting volunteers who are interested in participating in a brain-spinal cord-muscle response training study that aims to better understand the changes that take place in the nervous system as a result of this type of training. After spinal cord injury, brain-to-muscle connections are often interrupted. Because these connections are important in movement control, when they are not working well, movements may be disturbed. Researchers have found that people can learn to strengthen these connections through training. Strengthening these connections may be able to improve movement control and recovery after injuries.

Research participants will be asked to stand, sit, and walk during the study sessions. Electrodes are placed on the skin over leg muscles for monitoring muscle activity. For examining brain-to-muscle connections, the study team will use transcranial magnetic stimulation. The stimulation is applied over the head and will indirectly stimulate brain cells with little or no discomfort.

Participation in this study requires approximately three sessions per week for four months, followed by two to three sessions over another three months. Each session lasts approximately 1 hour.

Study Overview

• Status: Recruiting
• Conditions: Paralysis; Spinal Cord Injuries; Spasticity, Muscle; Neurological Injury
• Intervention / Treatment: Combination product: Operant Conditioning; Combination product: Control Group

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Blair Dellenbach, MSOT; Phone Number: 843-792-6313; Email: stecb@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Blair Dellenbach; Phone Number: 843-792-6313; Email: stecb@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Neurologically stable (>1 year post SCI)
• Medical clearance to participate
• Ability to ambulate at least 10 m with or without an assistive device (except for parallel bars)
• Signs of weak ankle dorsiflexion at least unilaterally
• Expectation that current medication will be maintained without change for at least 3 months; stable use of anti-spasticity medication is accepted

Exclusion Criteria:

• motoneuron injury
• known cardiac condition (e.g., history of myocardial infarction, congestive heart failure, pacemaker use)
• medically unstable condition
• cognitive impairment
• history of epileptic seizures
• metal implants in the cranium
• implanted biomedical device in or above the ches (e.g., a cardiac pacemaker, cochlear implant)
• no measurable MEP elicited
• unable to produce any voluntary TA EMG activity
• extensive use of functional electrical stimulation to the leg on a daily basis
• pregnancy (due to changes in weight and posture and potential medical instability)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Up-conditioning (UC) Group	Combination product: Operant Conditioning; This is a training intervention in which the brain-spinal cord-muscle pathways are strengthened in individuals with incomplete spinal cord injury. Transcranial magnetic stimulation (TMS), a type of brain stimulation, will be used to elicit a muscle response from the tibialis anterior (TA), the muscle that lifts your toes and foot.
Sham Comparator: Control (NC) Group	Combination product: Control Group; This is the control intervention, or the non-conditioning group. Transcranial magnetic stimulation (TMS), a type of brain stimulation, will be used to elicit a muscle response from the tibialis anterior (TA), the muscle that lifts your toes and foot.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the excitability/strength of the brain-spinal cord-muscle pathway at the brain level as measured by the MEP recruitment curve--Studied Leg	An increased maximum MEP size (mV) would indicate increased excitability/strength of the brain-spinal cord-muscle pathway	Baseline through 3 months post intervention
Change in the cortical map of the Tibialis Anterior: identifying the size (cm2) of the area of the brain that controls the tibialis anterior, the muscle that raises the toes and foot--Studied Leg	Reorganization of the TA cortical map would suggest that operant conditioning of the muscle response changes the brain. Knowing if and how the brain changes will help investigators understand the potential impact of this type of training.	Baseline through 3 months post intervention
Change in the excitability/strength of the brain-spinal cord-muscle pathway at the spinal-cord level as measured by the Cervicomedullary MEP (CMEP) size--Studied Leg	An increase in the size of the CMEP (mV) elicited at a fixed stimulus intensity would indicate increased excitability/strength at the spinal cord level	Baseline through 3 months post intervention
Change in excitability of the excitability of the brain as measured by Short Interval Intra-cortical Inhibition (SICI)	Decreased SICI indicates increased excitability in the brain	Baseline through 3 months post intervention
Change in reflex activity as measured by the H-reflex amplitude (mV) in response to nerve stimulation--Studied Leg	Decreased H-reflex amplitude indicates reduced reflex activity and a more normal reflex response to muscle activity	Baseline through 3 months post intervention
Change in excitability/strength of the spinal cord-muscle pathway as measured by Change in F-wave amplitude (mV) and F-wave occurrence (out of 30 trials) in response to nerve stimulation--Studied Leg	Increased F-wave amplitude and/or occurrence indicates increased excitability/strength of the spinal cord-muscle pathway	Baseline through 3 months post intervention
Change in the ability to activate the muscle that lifts the toes during the swing-phase of walking as measured by tibialis anterior EMG amplitude (mv)--Studied Leg	Increased EMG amplitude indicates greater activation of the muscle, which could indicate an increased ability to lift the toes during the swing-phase of walking	Baseline through 3 months post intervention
Change in ankle joint motion during walking (deg)--Studied Leg	Ankle range of motion over the step cycle (in deg); Ankle peak flexion angle (in deg); Ankle angle at foot contact (in deg); Median ankle angle over the step cycle (in deg)	Baseline through 3 months post intervention
Change in walking speed (m/s) as measured by the 10-meter walk test	Speed of the participant's fastest comfortable walking speed across 10 meters. Decreased time (sec) demonstrates increased walking speed (m/s)	Baseline through 3 months post intervention
Change in walking distance (meters) as measured by the 6-minute walk test	The distance walked in 6 minutes in measured. The participant is asked to walk at his/her fastest comfortable speed on an indoor walkway.	Baseline through 3 months post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ankle joint motion during walking (deg)--Studied Leg	Ankle range of motion over the step cycle (in deg); Ankle peak flexion angle (in deg); Ankle angle at foot contact (in deg); Median ankle angle over the step cycle (in deg)	Baseline through 3 months post intervention
Change in the excitability/strength of the brain-spinal cord-muscle pathway at the brain level as measured by the MEP recruitment curve--Contralateral Leg	An increased maximum MEP size (mV) would indicate increased excitability/strength of the brain-spinal cord-muscle pathway	Baseline through 3 months post intervention
Change in the cortical map of the Tibialis Anterior: identifying the size (cm2) of the area of the brain that controls the tibialis anterior, the muscle that raises the toes and foot--Contralateral Leg	Reorganization of the TA cortical map would suggest that operant conditioning of the muscle response changes the brain. Knowing if and how the brain changes will help investigators understand the potential impact of this type of training.	Baseline through 3 months post intervention
Change in the excitability/strength of the brain-spinal cord-muscle pathway at the spinal-cord level as measured by the Cervicomedullary MEP (CMEP) size--Contralateral Leg	An increase in the size of the CMEP (mV) elicited at a fixed stimulus intensity would indicate increased excitability/strength at the spinal cord level	Baseline through 3 months post intervention
Change in reflex activity as measured by the H-reflex amplitude (mV) in response to nerve stimulation--Contralateral Leg	Decreased H-reflex amplitude indicates reduced reflex activity and a more normal reflex response to muscle activity	Baseline through 3 months post intervention
Change in excitability/strength of the spinal cord-muscle pathway as measured by Change in F-wave amplitude (mV) and F-wave occurrence (out of 30 trials) in response to nerve stimulation--Contralateral Leg	Increased F-wave amplitude and/or occurrence indicates increased excitability/strength of the spinal cord-muscle pathway	Baseline through 3 months post intervention
Change in the ability to activate the muscle that lifts the toes during the swing-phase of walking as measured by tibialis anterior EMG amplitude (mv)--Contralateral Leg	Increased EMG amplitude indicates greater activation of the muscle, which could indicate an increased ability to lift the toes during the swing-phase of walking	Baseline through 3 months post intervention
Change in knee joint motion during walking (deg)--Both Legs	Knee range of motion over the step cycle (in deg); knee peak flexion angle (in deg); knee peak extension angle (in deg); knee angle at foot contact (in deg); median knee angle over the step cycle (in deg)	Baseline through 3 months post intervention
Change in hip joint motion during walking (deg)--Both Legs	Hip range of motion over the step cycle (in deg); hip peak flexion angle (in deg); hip peak extension angle (in deg); hip angle at foot contact (in deg); median hip angle over the step cycle (in deg)	Baseline through 3 months post intervention
Changes in reflexes and muscle activation during walking as measured by H-reflex size and cutaneous reflex size	Decreased H-reflex response and decreased radiating threshold of the cutaneous reflex would reflect reflex activity that is more similar to individuals without neurological injury	Baseline through 3 months post intervention

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Aiko K Thompson, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2021
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: February 24, 2020
• First Posted (Actual): February 26, 2020

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Neuroplasticity; Corticospinal Tract
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Spinal Cord Diseases; Muscle Hypertonia; Wounds and Injuries; Paralysis; Spinal Cord Injuries; Muscle Spasticity; Trauma, Nervous System
• Other Study ID Numbers: 00091457; 1R01NS114279-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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