The goal of this clinical trial is to learn if non-invasive spinal cord stimulation intervention improves blood pressure regulation in individuals with chronic spinal cord injury. The main questions it aims to answer are:

• Can site specific spinal cord stimulation enhance blood pressure regulation?
• Does this stimulation affect enzymes responsible for blood pressure regulation? Researchers will stimulate different sites of spinal cord and compare to see if site-specific stimulation provide blood pressure stability.

Participants will have up to six pairs of self-adhesive conductive electrodes placed on the skin over the spinal cord (midline and/or just to the left and right of midline) as cathodes and up to six pairs of self-adhesive electrodes located symmetrically on the skin over the iliac crests, clavicles, shoulders, and/or abdominal muscles (left and right of the umbilicus) as anodes for stimulation of the spinal cord.

This study introduces a novel mechanistic framework for treating and understanding autonomic regulation of blood pressure in SCI. The central hypothesis is that targeted specific scTS will restore cardiovascular homeostasis by strengthening complex neurohormonal pathways of blood pressure control. We expect that changes in these physiological and biochemical parameters will translate into greater cardiovascular stability, reduced frequency and severity of hypotensive and hypertensive episodes, and enhanced quality of life for individuals with SCI in individuals with Spinal Cord Injury (SCI) at the neurological level T1 and above, and more than one year after injury. The study team will recruit up to forty participants with the goal of fifteen participants to complete study interventions and assessments through the second follow-up visit. After recruitment and screening, primary and secondary outcome measures will be obtained at the following time points: 1) Pre-intervention (inclusive of randomization and mapping), 2) Session 20, 3) Mid-Intervention, 4) Session 60, 5) post-intervention, 6) 1st Follow-Up (8 weeks after post-intervention), and 7) 2nd Follow-Up (16 weeks after post-intervention). Participants will be asked to complete eighty sessions over a 16 to 20-week period, delivered 4 to 5 days per week for one hour each day. The stimulation will be delivered with frequency of up to 100 Hz, with incrementally increased intensity up to 200 mA to the participant for 80 sessions 1 hour long spanning 16 to 20 weeks.

Inclusion Criteria:

• At least 18 years old,
• Stable medical condition,
• Non-progression SCI (no negative change in the neurological level and motor-completeness assess during screening when compared to the neurological status assessed at 6-month period after injury or at least 6 months prior to the screening),
• Motor-complete SCI according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade "A," "B," or "C" above T1 spinal level according to the ASIA International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Neurological Level of Injury (NLI),
• Sustained SCI at least 12 months prior to entering the study,
• Evidence of symptomatic hypotension as determined by a total score >0 on the Orthostatic Hypotension Symptom Assessment (OSHA),
• Normal renal function as defined by eGFR > 59 ml/min/1.73, creatinine value within the range of 0.6-1.2 mg/dl, and BUN values within the range of 7-18 mg/dl,
• Competent to give informed consent for the research protocol,
• Able to understand instructions.

Exclusion Criteria:

• Major pulmonary or cardiovascular disease unrelated to SCI,
• Ventilator dependence,
• Painful musculoskeletal dysfunction that might interfere with testing or stimulation,
• Unhealed fracture that might interfere with testing or stimulation,
• Unhealed contracture that might interfere with testing or stimulation,
• Unhealed pressure sore that might interfere with testing or stimulation,
• Untreated clinically significant depression or psychiatric disorders,
• Ongoing drug abuse,
• Malignancy ,
• Class III obesity (BMI >40) and at least one co-morbidity thereof: a) Type 2 diabetes as defined by ≥6.5% level on two separate glycated hemoglobin (A1C) tests, b) hypertension as defined by consistent blood pressure readings of ≥140/90 mmHg or taking medication for blood pressure,
• Acute or chronic obstructive deep vein thrombosis,
• Secondary hypotension unrelated to SCI (anemia, hypervolemia, endocrine and neurological diseases),
• Major esophageal/gastrointestinal problem,
• Currently pregnant (females of childbearing potential only),
• Other major medical illness contraindicated for testing or stimulation.

Plans for sharing individual participant data are currently under consideration. Decisions regarding data sharing will be made following study completion in accordance with institutional guidelines and participant privacy protections.