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RecruitingNCT07504055Updated Apr 28, 2026

Non-invasive Spinal Cord Stimulation and Blood Pressure Regulation After Spinal Cord Injury

An interventional study of Spinal Cord Transcutaneous Stimulation in Spinal Cord Injury, Orthostatic Hypertension and Autonomic Dysreflexia, sponsored by University of Louisville. Recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-28.

Sponsored by University of Louisville · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Spinal Cord Injury
  • Orthostatic Hypertension
  • Autonomic Dysreflexia
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (estimated)

Study arms

  • Active comparator
    CV-scTS 1

    The participants in this arm will receive spinal cord stimulation at the thoracolumbar level (T10 to L1 spinal cord levels) targeted for blood pressure regulation. There will be mapping sessions where stimulation will be provided to assess the impact on functional outcomes and to refine stimulation parameters for training. Using multi-variant combinations of electrode locations and different electrical configurations, the stimulation will be delivered with frequency of up to 100 Hz, with incrementally increased intensity up to 200mA. During stimulation interventions, 5 mA-sub-motor threshold intensity with mapping-identified frequency, pulse width, and intensity will be delivered during interventional bouts.

    Device: Spinal Cord Transcutaneous Stimulation

  • Active comparator
    CV-scTS 2

    The participants in this arm will receive spinal cord stimulation at the lumbosacral level (L1 to S1 spinal cord levels) targeted for blood pressure regulation. There will be mapping sessions where stimulation will be provided to assess the impact on functional outcomes and to refine stimulation parameters for training. Using multi-variant combinations of electrode locations and different electrical configurations, the stimulation will be delivered with frequency of up to 100 Hz, with incrementally increased intensity up to 200mA. During stimulation interventions, 5 mA-sub-motor threshold intensity with mapping-identified frequency, pulse width, and intensity will be delivered during interventional bouts.

    Device: Spinal Cord Transcutaneous Stimulation

  • Active comparator
    Resp-scTS

    Qualifying participants of NCT06019949 (IRB #23.0570) randomized to the respiratory stimulation alone intervention group (Resp-scTS) will be invited to participate in this study to collect additional outcome measures. Overlapping assessments will be shared between the two studies. Participants in this arm will receive spinal cord stimulation at the thoracic level (T1 to T9 spinal cord levels) targeted for respiratory function. There will be mapping sessions where stimulation will be provided to assess the impact on functional outcomes and to refine stimulation parameters for training. Using multi-variant combinations of electrode locations and different electrical configurations, the stimulation will be delivered with frequency of up to 100 Hz, with incrementally increased intensity up to 200mA. During stimulation interventions, 5 mA-sub-motor threshold intensity with mapping-identified frequency, pulse width, and intensity will be delivered during interventional bouts.

    Device: Spinal Cord Transcutaneous Stimulation

Interventions

  • DeviceSpinal Cord Transcutaneous Stimulation

    Spinal Cord Transcutaneous Stimulation (scTS) will be administered using the Biostim/Neostim (Cosyma Inc., Denver CO) device. Up to six pairs of self-adhesive conductive electrodes will be 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. During scTS mapping sessions, stimulation will be provided to assess the impact on functional outcomes and to refine stimulation parameters for training (e.g., blood pressure modulation, respiratory function) targeted for each arm. Using multi-variant combinations of electrode locations and different electrical configurations, the stimulation will be delivered at a level specific to each arm with frequency of up to 100 Hz, with incrementally increased intensity up to 200 mA.

05

What researchers measure

Primary outcomes

  1. Baroreflex Sensitivity

    Baroreflex Sensitivity refers to the ability of the baroreflex mechanism in the body to sense changes in blood pressure and modulate heart rate and vascular tone accordingly. It is calculated as a linear regression of systolic blood pressure plotted against its corresponding R-R peaks on the electrocardiograph.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 weeks and 16-weeks follow-up period.

  2. Renal Artery Systolic Velocity (Right and Left)

    Renal Artery Systolic Velocity is the velocity of blood flow in the main renal artery supplying the kidneys. It will be obtained individually for right main renal artery and left main renal artery.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 weeks and 16-weeks follow-up period.

  3. Plasma Renin Activity

    Plasma Renin Activity is a biochemical blood test that measures the enzymatic activity of renin in the plasma. It is assessed by determining how effectively renin converts angiotensinogen to angiotensin I to evaluate the renin-angiotensin-aldosterone system (RAAS) activity.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

  4. Angiotensin Converting Enzyme

    The blood test for angiotensin converting enzyme (ACE) evaluates the concentration of ACE in the bloodstream, an enzyme that converts angiotensin I into angiotensin II, which helps regulate blood pressure by constricting small blood vessels.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

  5. Aldosterone

    An aldosterone blood test measures the hormone aldosterone in the blood to evaluate adrenal gland function and its impact on blood pressure and electrolyte balance.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

Secondary outcomes

  1. Complete Blood Count

    This test will evaluate various components of blood including hematocrit; hemoglobin; mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC); red cell distribution width (RDW); percentage and absolute differential counts; platelet count (PLT); red cell count (RBC); white blood cell count (WBC) for compounding effects.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

  2. Metabolic Panel

    This test will evaluate Blood Urea Nitrogen (BUN); BUN:creatinine ratio; calcium, chloride, creatinine, eGFR; glucose; potassium and sodium to check for compounding effects.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

  3. Lipid Panel

    This test will evaluate total cholesterol, high-density lipoprotein (HDL); low-density lipoprotein (LDL); triglycerides and very low-density lipoprotein (VLDL) in blood for to check for compounding effects.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

  4. Thyroid Panel

    This test will evaluate level of thyroid hormones in the blood to check for compounding effects.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #20; within 2 weeks after intervention #40; within 2 weeks after intervention #60; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 and 16-weeks follow-up.

  5. Incidence of Orthostatic Hypotension

    A pre-defined questionnaire in which participants will be asked to rate how severe their symptoms of low blood pressure are from 0 (none) to 10 (worst possible). The metrics include dizziness, lightheadedness, feeling faint, or feeling like you might black out; problems with vision (blurring, seeing spots, tunnel vision, etc.); weakness; fatigue; trouble concentrating; and head and neck discomfort.

    Time frame: Within 4 weeks before an intervention; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after weeks after 8 weeks and 16-weeks follow-up period.

06

Study locations

1 of 2 sites recruiting
  • Frazier Rehabilitation and Neuroscience Institute
    Louisville, Kentucky 40202, United States
    Not yet recruiting
  • Frazier Rehabilitation Institute
    Louisville, Kentucky 40202, United States
    Recruiting
07

References and documents

Publications

  • Itzkovich M, Gelernter I, Biering-Sorensen F, Weeks C, Laramee MT, Craven BC, Tonack M, Hitzig SL, Glaser E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J, Catz A. The Spinal Cord Independence Measure (SCIM) version III: reliability and validity in a multi-center international study. Disabil Rehabil. 2007 Dec 30;29(24):1926-33. doi: 10.1080/09638280601046302. Epub 2007 Mar 5. PubMed 17852230 ↗
  • Hubli M, Krassioukov AV. Ambulatory blood pressure monitoring in spinal cord injury: clinical practicability. J Neurotrauma. 2014 May 1;31(9):789-97. doi: 10.1089/neu.2013.3148. Epub 2014 Jan 30. PubMed 24175653 ↗
  • Aslan SC, Chopra MK, McKay WB, Folz RJ, Ovechkin AV. Evaluation of respiratory muscle activation using respiratory motor control assessment (RMCA) in individuals with chronic spinal cord injury. J Vis Exp. 2013 Jul 19;(77). doi: 10.3791/50178. PubMed 23912611 ↗
  • American Thoracic Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002 Aug 15;166(4):518-624. doi: 10.1164/rccm.166.4.518. No abstract available. PubMed 12186831 ↗
  • Ozer MN, Shannon SR. Renal sonography in asymptomatic persons with spinal cord injury: a cost-effectiveness analysis. Arch Phys Med Rehabil. 1991 Jan;72(1):35-7. PubMed 1898695 ↗
  • Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012 Apr;22(2):79-90. doi: 10.1007/s10286-011-0146-2. Epub 2011 Nov 2. PubMed 22045363 ↗
  • Osborn JW, Tyshynsky R, Vulchanova L. Function of Renal Nerves in Kidney Physiology and Pathophysiology. Annu Rev Physiol. 2021 Feb 10;83:429-450. doi: 10.1146/annurev-physiol-031620-091656. PubMed 33566672 ↗
  • Johns EJ, Kopp UC, DiBona GF. Neural control of renal function. Compr Physiol. 2011 Apr;1(2):731-67. doi: 10.1002/cphy.c100043. PubMed 23737201 ↗
  • Sata Y, Head GA, Denton K, May CN, Schlaich MP. Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension. Front Med (Lausanne). 2018 Mar 29;5:82. doi: 10.3389/fmed.2018.00082. eCollection 2018. PubMed 29651418 ↗
  • Ackermann, U., Regulation of arterial blood pressure. Surgery - Oxford International Edition, 2004. 22(5): p. 120a-120f.
  • Legg Ditterline BE, Aslan SC, Randall DC, Harkema SJ, Ovechkin AV. Baroreceptor reflex during forced expiratory maneuvers in individuals with chronic spinal cord injury. Respir Physiol Neurobiol. 2016 Jul 15;229:65-70. doi: 10.1016/j.resp.2016.04.006. Epub 2016 Apr 30. PubMed 27137412 ↗
  • Legg Ditterline BE, Aslan SC, Randall DC, Harkema SJ, Castillo C, Ovechkin AV. Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury. Arch Phys Med Rehabil. 2018 Mar;99(3):423-432. doi: 10.1016/j.apmr.2017.06.033. Epub 2017 Aug 9. PubMed 28802811 ↗
  • Aslan SC, Randall DC, Krassioukov AV, Phillips A, Ovechkin AV. Respiratory Training Improves Blood Pressure Regulation in Individuals With Chronic Spinal Cord Injury. Arch Phys Med Rehabil. 2016 Jun;97(6):964-73. doi: 10.1016/j.apmr.2015.11.018. Epub 2015 Dec 21. PubMed 26718236 ↗
  • Aslan SC, Randall DC, Donohue KD, Knapp CF, Patwardhan AR, McDowell SM, Taylor RF, Evans JM. Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt. Am J Physiol Regul Integr Comp Physiol. 2007 Mar;292(3):R1146-57. doi: 10.1152/ajpregu.00225.2006. Epub 2006 Nov 2. PubMed 17082357 ↗
  • Aslan SC, Legg Ditterline BE, Park MC, Angeli CA, Rejc E, Chen Y, Ovechkin AV, Krassioukov A, Harkema SJ. Epidural Spinal Cord Stimulation of Lumbosacral Networks Modulates Arterial Blood Pressure in Individuals With Spinal Cord Injury-Induced Cardiovascular Deficits. Front Physiol. 2018 May 18;9:565. doi: 10.3389/fphys.2018.00565. eCollection 2018. PubMed 29867586 ↗
  • McMullan S, Pilowsky PM. The effects of baroreceptor stimulation on central respiratory drive: a review. Respir Physiol Neurobiol. 2010 Nov 30;174(1-2):37-42. doi: 10.1016/j.resp.2010.07.009. Epub 2010 Jul 30. PubMed 20674807 ↗
  • Frisbie JH. Breathing and the support of blood pressure after spinal cord injury. Spinal Cord. 2005 Jul;43(7):406-7. doi: 10.1038/sj.sc.3101732. PubMed 15741979 ↗
  • Wecht JM, Harel NY, Guest J, Kirshblum SC, Forrest GF, Bloom O, Ovechkin AV, Harkema S. Cardiovascular Autonomic Dysfunction in Spinal Cord Injury: Epidemiology, Diagnosis, and Management. Semin Neurol. 2020 Oct;40(5):550-559. doi: 10.1055/s-0040-1713885. Epub 2020 Sep 9. PubMed 32906175 ↗
  • Weaver LC, Fleming JC, Mathias CJ, Krassioukov AV. Disordered cardiovascular control after spinal cord injury. Handb Clin Neurol. 2012;109:213-33. doi: 10.1016/B978-0-444-52137-8.00013-9. PubMed 23098715 ↗

Individual participant data

Plan to share: No — 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.

08

Registry details

Key details

Study ID
NCT07504055
Lead sponsor
University of Louisville
Collaborators
Kentucky Spinal Cord and Head Injury Research Board
Responsible party
Alexander V Ovechkin, MD, PhD (Professor, University of Louisville) — Principal investigator
First posted
Mar 31, 2026
Start date
Apr 1, 2026
Primary completion
Feb 2029 (estimated)
Completion
Feb 2029 (estimated)
Last update
Apr 28, 2026

Study contacts

Andrea M Willhite
Contact
andrea.willhite@louisville.edu
1-502-581-8675
Kristin Benton
Contact
kristin.benton@louisville.edu
1-502-581-8675
Alexander Ovechkin
principal investigator · University of Louisville

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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