Clinical trial NCT04105114: Transformation of Paralysis to Stepping
Official title: Transformation of Paraplegic Paralysis to Overground Stepping in Humans
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Spinal Cord Injuries
Keywords: Walking
Transcutaneous Stimulation
Locomotion
Paralysis
Buspirone
Motor Control
Spinal Stimulation
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: The National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2019-09-26
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Lower Extremity Electromyography, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Lower Extremity Kinematics, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Treadmill Electromyography Assessment, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Spinal Pathway Electrophysiology, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Voluntary Lower Extremity Angles, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Voluntary Lower Extremity Forces, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Body Temperature, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Blood Pressure, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Heart Rate, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Respiration Rate, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Dual-energy X-ray absorptiometry, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Acoustic Gastro-Intestinal Surveillance, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Bladder capacity, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Urodynamics, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Cognitive interference, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Assessment of verbal fluency, change over time
timeFrame: Before and after each study phase, 1 year per group.
Secondary outcomes:
measure: International Standards of Neurological Classification of Spinal Cord Injury, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Spinal Cord Injury Functional Ambulation Inventory, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Spinal Cord Independence Measure III, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Walking Index for Spinal Cord Injury-II, change over time
timeFrame: Before and after each study phase, 1 year per group.
measure: Ashworth Scale, change over time
timeFrame: Before and after each study phase, 1 year per group.
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Frazier Rehabilitation and Neuroscience Institute
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Alexander V Ovechkin, PhD
role: STUDY_DIRECTOR
References: