Transformation of Paralysis to Stepping

NCT04105114 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 19.04341R01NS102920-01A1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of the project is to develop multiple noninvasive neuromodulatory strategies to facilitate full weight bearing stepping overground in people with paralysis. We will determine the effectiveness of combining noninvasive spinal cord stimulation and the administration of buspirone (a monoaminergic agonist) in facilitating locomotor activity in a gravity-neutral apparatus, during body weight supported stepping on a treadmill, when stepping overground, or during full weight bearing stepping overground in a rolling walker. Our objective is to identify the experimental variables that define the efficacy of these novel neuromodulatory techniques over a 5 year period in 15 participants with severe spinal cord injury who are at least one year post-injury.

Conditions

Spinal Cord Injuries

Keywords

Walking; Transcutaneous Stimulation; Locomotion; Paralysis; Buspirone; Motor Control; Spinal Stimulation

Outcome Measures

Primary Outcomes (16)

• Lower Extremity Electromyography, change over time

  Assessment of muscle activity, measured by electromyography, while the leg is suspended in a gravity neutral position.

  Before and after each study phase, 1 year per group.

• Lower Extremity Kinematics, change over time

  Assessment of low extremity 3D position, measured by motion analysis system, while the leg is suspended in a gravity neutral position.

  Before and after each study phase, 1 year per group.

• Treadmill Electromyography Assessment, change over time

  Muscle activity, measured by electromyography, will be recorded during weight supported stepping on a treadmill.

  Before and after each study phase, 1 year per group.

• Spinal Pathway Electrophysiology, change over time

  Evoked potentials in the lower extremities will recorded in response to nerve or spinal stimulation.

  Before and after each study phase, 1 year per group.

• Voluntary Lower Extremity Angles, change over time

  Assessments of knee, ankle, and toe movements will be performed by measuring angles produced during flexion and extension. The same units of measure will be used for each part of the leg.

  Before and after each study phase, 1 year per group.

• Voluntary Lower Extremity Forces, change over time

  Assessments of knee, ankle, and toe forces during movements will be performed by measuring forces produced during flexion and extension. The same units of measure will be used for each part of the leg.

  Before and after each study phase, 1 year per group.

• Body Temperature, change over time

  We will measure body temperature using standard methods to assess values at rest and during exercise.

  Before and after each study phase, 1 year per group.

• Blood Pressure, change over time

  We will measure blood pressure (systolic and diastolic) using standard methods to assess values at rest and during exercise.

  Before and after each study phase, 1 year per group.

• Heart Rate, change over time

  We will measure the heart rate using standard electrocardiography to assess values at rest and during exercise.

  Before and after each study phase, 1 year per group.

• Respiration Rate, change over time

  We will measure respiratory rate using standard methods to assess values at rest and during exercise.

  Before and after each study phase, 1 year per group.

• Dual-energy X-ray absorptiometry, change over time

  We will use dual-energy X-ray absorptiometry to measure bone and soft tissue density.

  Before and after each study phase, 1 year per group.

• Acoustic Gastro-Intestinal Surveillance, change over time

  We will use non-invasive sensors placed on the abdomen to detect signals related to the digestive state.

  Before and after each study phase, 1 year per group.

• Bladder capacity, change over time

  We will use a standard technique to measure bladder volume change during voiding.

  Before and after each study phase, 1 year per group.

• Urodynamics, change over time

  We will use a standard technique to measure the abdominal pressure change during voiding.

  Before and after each study phase, 1 year per group.

• Cognitive interference, change over time

  A cognitive assessment using Stroop test will be administered to assess cognitive function during stress.

  Before and after each study phase, 1 year per group.

• Assessment of verbal fluency, change over time

  Controlled Oral Word Association Test (COWAT) will be administered to assess verbal fluency that measures ability of spontaneous production of words.

  Before and after each study phase, 1 year per group.

Secondary Outcomes (5)

• International Standards of Neurological Classification of Spinal Cord Injury, change over time

  Before and after each study phase, 1 year per group.

• Spinal Cord Injury Functional Ambulation Inventory, change over time

  Before and after each study phase, 1 year per group.

• Spinal Cord Independence Measure III, change over time

  Before and after each study phase, 1 year per group.

• Walking Index for Spinal Cord Injury-II, change over time

  Before and after each study phase, 1 year per group.

• Ashworth Scale, change over time

  Before and after each study phase, 1 year per group.

Study Arms (3)

Complete Spinal Cord Injury - Gravity Neutral Stepping

EXPERIMENTAL

Group 1 will begin with a 3-4-month preparation phase and up to 12 sessions in the gravity neutral device (GND) will occur. The training sessions in the GND will be used to obtain the optimal stimulation parameters. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. This will be done in the GND in the presence of stimulation. Afterwards, Intervention 2 will include the same training procedures with the addition of Buspirone or Placebo in a cross-over fashion halfway through this phase.

Drug: Buspirone; Device: Non-invasive Spinal Cord Stimulation; Device: Gravity Neutral Device; Device: Body Weight Supported Treadmill Training

Complete Spinal Cord Injury - Overground Stepping

EXPERIMENTAL

Group 2 will begin with a 3-month preparation phase and up to 12 sessions of overground stepping. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours overground training, in the presence of stimulation and Buspirone/placebo. The second phase will include the same training procedures except for the removal of Buspirone/placebo administration. The third phase will include sessions twice per week of the overground with stimulation and one day per week using a rolling walker with stimulation. The last phase will include 2 sessions per week using the rolling walker in the presence of stimulation and Buspirone/placebo.

Drug: Buspirone; Device: Non-invasive Spinal Cord Stimulation; Device: Overground stepping; Device: Rolling Walker

Incomplete Spinal Cord Injury - Overground Stepping

EXPERIMENTAL

Group 3 will begin with a 3-month preparation phase and up to 12 sessions stepping overground. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. The overground session will use the rolling walker in the presence of stimulation. Afterwards, the second phase will include the same training procedures with the addition of Buspirone/placebo.

Drug: Buspirone; Device: Non-invasive Spinal Cord Stimulation; Device: Overground stepping; Device: Rolling Walker

Interventions

Buspirone DRUG

Oral Buspirone 7.5mg - 10mg daily during the treatment phase.

Also known as: Buspar

Complete Spinal Cord Injury - Gravity Neutral Stepping; Complete Spinal Cord Injury - Overground Stepping; Incomplete Spinal Cord Injury - Overground Stepping

Gravity Neutral Device DEVICE

This device is used to train and assess non-weight bearing stepping movements. When using the device, participants will be lying on their side with their legs suspended off the end of a table supported by small slings that are anchored securely to the apparatus.

Complete Spinal Cord Injury - Gravity Neutral Stepping

Non-invasive Spinal Cord Stimulation DEVICE

A non-invasive transcutaneous electrical spinal cord stimulator, which can be used a multiple spinal locations.

Complete Spinal Cord Injury - Gravity Neutral Stepping; Complete Spinal Cord Injury - Overground Stepping; Incomplete Spinal Cord Injury - Overground Stepping

Overground stepping DEVICE

This intervention is designed to assist people with neurological injuries for balance, standing, and stepping overground.

Complete Spinal Cord Injury - Overground Stepping; Incomplete Spinal Cord Injury - Overground Stepping

Body Weight Supported Treadmill Training DEVICE

Participants will be supported by a special harness while they are stepping on a treadmill. Trained technicians or therapists will be assist the trunk and legs during stepping as needed.

Complete Spinal Cord Injury - Gravity Neutral Stepping

Rolling Walker DEVICE

A standard rolling walker will be used for balance support and stability during stepping overground.

Complete Spinal Cord Injury - Overground Stepping; Incomplete Spinal Cord Injury - Overground Stepping

Eligibility Criteria

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

You may qualify if:

• Participants with Motor Complete SCI:
• years old,
• Stable medical condition,
• At least 1-year post-injury,
• Non-progressive SCI,
• Motor complete paraplegia: Unable to voluntarily move any joint of the lower limbs,
• Inability to walk independently due to SCI,
• Presence of active spinally evoked responses over the lumbo-sacral spinal cord using spinal Cord Transcutaneous Stimulation (scTS).
• Participants with Motor Incomplete SCI:
• years old,
• Stable medical condition,
• At least 1-year post-injury,
• Non-progressive SCI,
• Motor incomplete paraplegia: Able to voluntarily move at least 1 joint of the lower limbs bilaterally,
• Inability to walk independently in the community due to SCI,

You may not qualify if:

• Untreated pressure sores,
• Unhealed bone fractures,
• Untreated active urinary tract infections,
• Peripheral lower limb neuropathies unrelated to SCI,
• Seizure disorders,
• Cardiopulmonary disease unrelated to SCI,
• Untreated anemia,
• Ventilator dependency,
• Female participants: Pregnant or planning to become pregnant during the time course of study, or nursing,
• Healing wounds/surgical sites along the spine, levels T9-L5,
• Anti-spasticity implantable pumps,
• Untreated clinically significant depression, psychiatric disorders, or ongoing drug abuse,
• Colostomy bag, urostomy,
• Individuals with abnormal blood panel results related to hepatic function, Individuals with abnormal estimated glomerular filtration rate (eGFR) and increase Creatinine Clearance (CrCl) levels above the normal range,
• Individuals unwilling or unable to wean from drug(s) that interact(s) with buspirone, such as: Monoamine oxidase inhibitors (MAOIs) - Selegiline (Emsam), Isocarboxazid (Marplan), Phenelzein (Nardil), and Tranylcypromine (Parnate).

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Louisville: lead

Study Sites (1)

Frazier Rehabilitation and Neuroscience Institute

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Paralysis

Interventions

Buspirone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Study Officials

• Alexander V Ovechkin, PhD

  University of Louisville

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, research staff, or participants during the Treatment Phase. The following study procedures will be in place to ensure double-blind administration of study treatments. Access to the randomization code will be strictly controlled. * Packaging and labeling of test and control treatments will be identical to maintain the blind. * The study blind will be broken on completion of the clinical study and after the study database has been locked. BuSpar (buspirone) and matching placebo tablets (2x/day) will be obtained and dispensed by the investigational pharmacy. Study drug and placebo will be labeled with the required FDA warning statement, the protocol number, a treatment number, the name of the sponsors, and directions for patient use and storage.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a double blinded crossover study with three experimental groups. Each group will receive a combination of activity based neuromodulation interventions while receiving oral Buspirone or placebo. The crossover between drug or placebo administration will occur at the study phase midpoint.

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: September 26, 2019
• Study Start: September 30, 2019
• Primary Completion: August 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)