Transformation of Paraplegic Paralysis to Overground Stepping in Humans

19.0434

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.

2019-09-30

2024-08-31

2027-12-31

Recruiting

Early phase I

15

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': '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.', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': '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.\n\n* Packaging and labeling of test and control treatments will be identical to maintain the blind.\n* The study blind will be broken on completion of the clinical study and after the study database has been locked.\n\nBuSpar (buspirone) and matching placebo tablets (2x/day) will be obtained and dispensed by the investigational pharmacy.\n\nStudy 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.', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 15, 'type': 'ESTIMATED'}}

2024-02-28