Spinal Stimulation + Buspirone for Paralysis

Overseen By Andrea Willhite, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Louisville

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 18

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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 in an assistive robotic exoskeleton, 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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, if you are on monoamine oxidase inhibitors, you must stop them at least 2 weeks before starting buspirone. Other medications that interact with buspirone may also need to be discontinued.

What data supports the effectiveness of this treatment for paralysis?

Research shows that body weight-supported treadmill training (BWSTT) can improve walking ability and muscle power in patients with neurological injuries, such as multiple sclerosis and spinal cord injury. This suggests that BWSTT, as part of the treatment, may help improve mobility in patients with paralysis. ^{1 2 3 4 5}

Is body weight-supported treadmill training (BWSTT) safe for humans?

Body weight-supported treadmill training (BWSTT) has been used in humans for rehabilitation, and studies suggest it is generally safe, although its effectiveness compared to other methods is still being evaluated. ^{1 2 3 6 7}

How is the Spinal Stimulation + Buspirone treatment for paralysis different from other treatments?

This treatment is unique because it combines spinal stimulation with Buspirone, a drug typically used for anxiety, alongside advanced physical therapies like robotic exoskeletons and body-weight-supported treadmill training. This combination aims to enhance walking ability by leveraging both neurological stimulation and physical support, which is different from traditional therapies that often focus on one aspect alone. ^{1 3 4 8 9}

Research Team

Alexander V Ovechkin, PhD

Principal Investigator

University of Louisville

Eligibility Criteria

This trial is for adults aged 18-65 with stable spinal cord injuries (AIS grade A, B, or C) that occurred over a year ago. Participants must not be on anti-spasticity meds or MAO inhibitors and should have active responses in their lower spine to stimulation. Exclusions include those with certain health conditions like unhealed fractures, infections, severe diseases unrelated to the injury, pregnancy, drug abuse issues, and some medication interactions.

Inclusion Criteria

I am not on any medication for muscle stiffness.

My spinal cord injury is between T1 and T8.

My spinal cord injury is stable and classified as A, B, or C.

Exclusion Criteria

I currently have an untreated urinary tract infection.

I have nerve damage in my legs.

I am healing from spine surgery between my mid-back and lower back.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation

Participants undergo a preparation phase with up to 12 sessions in the Ekso device or gravity neutral device to determine optimal stimulation parameters

3-4 months

Up to 12 sessions

Intervention Phase 1

Participants receive training sessions 3 days/week for approximately 2 hours in the presence of stimulation and Buspirone/placebo

Varies per group

3 visits per week

Intervention Phase 2

Continuation of training with the same procedures, with or without Buspirone/placebo

Varies per group

3 visits per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Assistive Robotic Exoskeleton
• Body Weight Supported Treadmill Training
• Buspirone
• Gravity Neutral Device
• Non-invasive Spinal Cord Stimulation
• Rolling Walker

Trial Overview The study tests if non-invasive spinal stimulation combined with buspirone can help people with paralysis step using different supports: gravity-neutral devices, treadmills with body support, robotic exoskeletons by Ekso Bionics or rolling walkers. It's a five-year study involving 15 participants to find out which techniques work best.

Participant Groups

Group I: Incomplete Spinal Cord Injury - Overground Stepping Experimental Treatment 4 Interventions

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

Group II: Complete Spinal Cord Injury - Gravity Neutral Stepping Experimental Treatment 4 Interventions

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.

Group III: Complete Spinal Cord Injury - Exoskeleton Assisted Stepping Experimental Treatment 4 Interventions

Group 2 will begin with a 3-month preparation phase and up to 12 sessions in the Ekso device stepping overground. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours in the Ekso overground, 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 in the Ekso 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 and one day per week in the Ekso, both in the presence of stimulation and Buspirone/placebo.

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

The National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1

Recruited

20+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

In a six-week study involving 20 multiple sclerosis patients, robot-assisted body-weight-supported treadmill training significantly improved the torque of both hip and knee joint muscles, enhancing lower limb muscle power.

This training led to better walking ability for patients, allowing them to walk with less effort and reduced reliance on caregivers, suggesting its potential as an effective rehabilitation method for gait dysfunction in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-Assisted Body-Weight-Supported Treadmill Training in Gait Impairment in Multiple Sclerosis Patients: A Pilot Study. Łyp, M., Stanisławska, I., Witek, B., et al.[2019]

A study involving four men with motor-incomplete spinal cord injury showed that 12 weeks of body weight-supported treadmill training (BWSTT) led to changes in brain activity, indicating potential supraspinal reorganization.

fMRI results revealed increased activation in sensorimotor and cerebellar regions after BWSTT, suggesting that this rehabilitation strategy not only improves locomotion but also enhances brain function related to movement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in supraspinal activation patterns following robotic locomotor therapy in motor-incomplete spinal cord injury. Winchester, P., McColl, R., Querry, R., et al.[2022]

A six-week body weight-support treadmill training (BWSTT) program significantly improved center-of-mass control in chronic incomplete spinal cord injury (iSCI) patients, as indicated by changes in the instrumented sway test results.

However, the BWSTT program did not lead to improvements in gait independence, as measured by the Walking Index Spinal Cord Injury (WISCI) II test scores, suggesting that while balance may improve, it does not necessarily translate to better walking ability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of body weight-support treadmill training on postural sway and gait independence in patients with chronic spinal cord injury. Covarrubias-Escudero, F., Rivera-Lillo, G., Torres-Castro, R., et al.[2020]

In a study involving 11 patients with incomplete spinal cord injury, patient-cooperative robot-aided gait training led to greater kinematic variability and increased muscle activity compared to non-cooperative training, suggesting enhanced engagement during rehabilitation.

The patient-cooperative approach, which allowed for free timing of movements and individually adjusted support, resulted in a more active participation from patients, indicating it may be a more effective method for gait rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-cooperative control increases active participation of individuals with SCI during robot-aided gait training. Duschau-Wicke, A., Caprez, A., Riener, R.[2021]

Body weight supported treadmill training significantly improves walking cadence, speed, and endurance in individuals with incomplete spinal cord injuries compared to conventional training methods, based on a review of six clinical trials from 2007 to 2019.

While this training method enhances certain aspects of gait, improvements in balance, functionality, and muscle strength are not significantly better than those achieved through conventional rehabilitation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treadmill training with partial body weight support in subjects with incomplete spinal cord injury: a systematic review]. Escribano-Ardura, S., Cuesta-Gómez, A., Fernández-González, P., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Robot-Assisted Body-Weight-Supported Treadmill Training in Gait Impairment in Multiple Sclerosis Patients: A Pilot Study. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Changes in supraspinal activation patterns following robotic locomotor therapy in motor-incomplete spinal cord injury. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

What Did We Learn from the Animal Studies of Body Weight-Supported Treadmill Training and Where Do We Go from Here? [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Robotic-assisted, body-weight-supported treadmill training in individuals following motor incomplete spinal cord injury. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effects of body weight-support treadmill training on postural sway and gait independence in patients with chronic spinal cord injury. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Should body weight-supported treadmill training and robotic-assistive steppers for locomotor training trot back to the starting gate? [2022]

7. England pubmed.ncbi.nlm.nih.gov

Patient-cooperative control increases active participation of individuals with SCI during robot-aided gait training. [2021]

8. Spain pubmed.ncbi.nlm.nih.gov

[Treadmill training with partial body weight support in subjects with incomplete spinal cord injury: a systematic review]. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of training methods to improve walking in persons with chronic spinal cord injury: a randomized clinical trial. [2021]