Transformation of Paralysis to Stepping

University of Louisville (UOFL)

Status and phase: Active, not recruiting; Early Phase 1

Conditions: Spinal Cord Injuries

Treatments: Drug: Buspirone; Device: Gravity Neutral Device; Device: Ekso Bionics Exoskeleton; Device: Body Weight Supported Treadmill Training; Device: Non-invasive Spinal Cord Stimulation; Device: Rolling Walker

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04105114

19.0434

1R01NS102920-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

Aim 1: Define the relative effectiveness of transcutaneous electrical stimulation at multiple stimulation spinal sites and oral Buspirone in facilitating nonweight-bearing (gravity neutral device, GND) and weight-bearing (treadmill) stepping in individuals with chronic motor complete paralysis.

Aim 1.1: Define the relative effectiveness of transcutaneous electrical stimulation at multiple spinal sites to facilitate non-weight-bearing (GND) and weight-bearing (treadmill) stepping in spinal cord injury subjects.

Aim 1.2: Define the relative effectiveness of transcutaneous electrical stimulation at multiple spinal sites plus oral Buspirone to facilitate nonweight-bearing (gravity neutral device, GND) and weight-bearing (treadmill) stepping in spinal cord injury subjects.

Aim 2: Determine the relative effectiveness of Ekso-technology combined with transcutaneous electrical stimulation and/or oral Buspirone in lowering the robotic assistance and enhancing the ability to step self-assisted in a rolling walker during over-ground stepping in individuals with a chronic, severe (AIS A/B) spinal injury.

Aim 3: Determine the relative effectiveness of Ekso-technology combined with transcutaneous electrical stimulation and/or oral Buspirone in lowering the robotic assistance and enhancing the ability to step self-assisted in a rolling walker during over-ground stepping in individuals with motor incomplete (AIS C) paralysis.

Enrollment: 15 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Ages 18-65 years old;
2. Stable medical condition;
3. More than 12 month's post injury;
4. Non-progressive spinal cord injury, AIS grade of A, B or C;
5. Neurological level of injury below T1 and above T8;
6. Not taking anti-spasticity medications;
7. Presence of active spinally evoked responses over the lumbo-sacral spinal cord using spinal stimulation;
8. Discontinuation of monoamine oxidase inhibitor (if applicable) for at least 2 weeks prior to initiation of treatment with buspirone.

Exclusion criteria

1. Active pressure sores;
2. Unhealed bone fractures;
3. Untreated active urinary tract infections;
4. Peripheral neuropathies;
5. Seizure disorders;
6. Cardiopulmonary disease unrelated to spinal cord injury;
7. Anemia;
8. Painful musculoskeletal dysfunction;
9. Contractures in the lower extremities;
10. Lower extremity hardware implantation;
11. Lower extremity lower motor neuron injury;
12. Previous unhealed lower extremity musculoskeletal injuries or disorders, prior to or in conjunction with spinal cord injury;
13. Ventilator dependency;
14. Pregnancy or nursing;
15. Healing wounds/surgical sites along the spine, levels T9-L5;
16. Anti-spasticity implantable pumps;
17. Clinically significant depression, psychiatric disorders, or ongoing drug abuse;
18. Implantable suprapubic catheters;
19. Individuals who are unable to support themselves and/or have difficulty standing;
20. Individuals with abnormal blood panel results related to hepatic function. Up to 10 ml of venous blood will be obtained for the testing;
21. Individuals with increased Creatinine Clearance (Clcr) levels above the normal range;
22. Individuals who are taking drug(s) that interact(s) with Buspirone (BuSpar): Monoamine oxidase inhibitors (MAOIs) - Selegiline (Emsam), Isocarboxazid (Marplan), Phenelzine (Nardil), and Tranylcypromine (Parnate) /these medications must discontinue for at least 2 weeks prior to initiating treatment with Buspirone/; Selective serotonin reuptake inhibitors (SSRIs) - Nefazodone (Serzone) and Trazodone (Oleptro); the blood thinner - Warfarin (Coumadin); Unti-seizure drugs: Phenytoin (Dilantin) and Carbamazepine (Tegretol); Benzodiazepines - Diazepam (Valium) and Triazolam (Halcion); Muscle relaxant - Cyclobenzaprine (Flexeril); Anti-fungal drugs - Itraconazole (Sporanox, Onmel), Itraconazole (Sporanox), and Ketoconazole (Nizoral); Antibiotics - Erythromycin (E.E.S., E-Mycin, Erythrocin) and Rifampin (Rifadin, Rimactane); Steroids (Prednisone and others); Anti-HIV drug - Ritonavir (Norvir); Anti-hypertensive drugs - Diltiazem (Cardizem) and Verapamil (Calan, Verelan, Covera-HS); Anti-psychotic drug - Haloperidol (Haldol);
23. Uncontrolled autonomic dysreflexia;
24. Osteoporosis.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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15 participants in 3 patient groups

Complete Spinal Cord Injury - Gravity Neutral Stepping

Experimental group

Description:

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.

Treatment:

Device: Non-invasive Spinal Cord Stimulation

Device: Body Weight Supported Treadmill Training

Device: Gravity Neutral Device

Drug: Buspirone

Complete Spinal Cord Injury - Exoskeleton Assisted Stepping

Experimental group

Description:

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.

Treatment:

Device: Rolling Walker

Device: Non-invasive Spinal Cord Stimulation

Device: Ekso Bionics Exoskeleton

Drug: Buspirone

Incomplete Spinal Cord Injury - Overground Stepping

Experimental group

Description:

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.

Treatment:

Device: Rolling Walker

Device: Non-invasive Spinal Cord Stimulation

Device: Ekso Bionics Exoskeleton

Drug: Buspirone