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

NCT07504055 | Recruiting DMC FDA Device

• 2 other identifiers: 25-17 KSCHIRTGR05737
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Spinal Cord Injury; Orthostatic Hypertension; Autonomic Dysreflexia

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

• 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.

  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.

• 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.

  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.

• 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.

  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.

• 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.

  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 (5)

• Complete Blood Count

  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.

• Metabolic Panel

  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.

• Lipid Panel

  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.

• Thyroid Panel

  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.

• Incidence of Orthostatic Hypotension

  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.

Study Arms (3)

CV-scTS 1

ACTIVE COMPARATOR

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

CV-scTS 2

ACTIVE COMPARATOR

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

Resp-scTS

ACTIVE COMPARATOR

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

Spinal Cord Transcutaneous Stimulation DEVICE

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.

CV-scTS 1; CV-scTS 2; Resp-scTS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Louisville: lead
• Kentucky Spinal Cord and Head Injury Research Board: collaborator

Study Sites (2)

Frazier Rehabilitation and Neuroscience Institute

Louisville, Kentucky, 40202, United States

NOT YET RECRUITING

Frazier Rehabilitation Institute

Louisville, Kentucky, 40202, United States

RECRUITING

Related Publications (19)

• 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.

  PMID: 17852230 RESULT

• 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.

  PMID: 24175653 RESULT

• 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):50178. doi: 10.3791/50178.

  PMID: 23912611 RESULT

• 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.

  PMID: 12186831 RESULT

• 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.

  PMID: 1898695 RESULT

• 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.

  PMID: 22045363 RESULT

• 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.

  PMID: 33566672 RESULT

• Johns EJ, Kopp UC, DiBona GF. Neural control of renal function. Compr Physiol. 2011 Apr;1(2):731-67. doi: 10.1002/cphy.c100043.

  PMID: 23737201 RESULT

• 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.

  PMID: 29651418 RESULT

• Ackermann, U., Regulation of arterial blood pressure. Surgery - Oxford International Edition, 2004. 22(5): p. 120a-120f.

  RESULT

• 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.

  PMID: 27137412 RESULT

• 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.

  PMID: 28802811 RESULT

• 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.

  PMID: 26718236 RESULT

• 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.

  PMID: 17082357 RESULT

• 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.

  PMID: 29867586 RESULT

• 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.

  PMID: 20674807 RESULT

• 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.

  PMID: 15741979 RESULT

• 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.

  PMID: 32906175 RESULT

• 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.

  PMID: 23098715 RESULT

Related Links

• Official website of the Centre for this Study

MeSH Terms

Conditions

Spinal Cord Injuries; Autonomic Dysreflexia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Autonomic Nervous System Diseases

Study Officials

• Alexander Ovechkin

  University of Louisville

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea M Willhite

CONTACT

1-502-581-8675; andrea.willhite@louisville.edu

Kristin Benton

CONTACT

1-502-581-8675; kristin.benton@louisville.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 31, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)