Physiological Changes Induced Through MEP Conditioning in People With SCI

NCT04286191 | Completed FDA Device

• 2 other identifiers: 000914571R01NS114279-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spinal Cord Injuries; Neurological Injury; Paralysis; Spasticity, Muscle

Keywords

Corticospinal Tract; Neuroplasticity

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (10)

• 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

  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

  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

  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

  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

  Baseline through 3 months post intervention

Study Arms (2)

Up-conditioning (UC) Group

EXPERIMENTAL

Combination Product: Operant Conditioning

Control (NC) Group

SHAM COMPARATOR

Combination Product: Control Group

Interventions

Operant Conditioning COMBINATION_PRODUCT

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.

Up-conditioning (UC) Group

Control Group COMBINATION_PRODUCT

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.

Control (NC) Group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Trauma, Nervous System; Paralysis; Muscle Spasticity

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Aiko K Thompson, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: February 26, 2020
• Study Start: February 22, 2021
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)