Spinal Cord Stimulation for Respiratory Rehabilitation in Patients With Chronic Spinal Cord Injury

NCT06019949 | Recruiting DMC FDA Device

• 2 other identifiers: 23.05701R01HL168294
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Respiratory complications are among the leading causes of death in patients with chronic spinal cord injury (SCI). Our previous work showed that pulmonary function can be improved by using our original respiratory training method. However, the effectiveness of this intervention is limited due to the disruption of brain-spinal connections and consequently lowered spinal cord activity below the injury level. Our recent studies showed that electrical stimulation of the spinal cord below the level of injury leads to increased ventilation which indicates activation of the spinal cord structures related to respiration. These findings indicate that spinal cord stimulation can be a promising therapeutic additive to the treatment. The goal of this study is to justify the establishment of a new direction in rehabilitation for patients with SCI by using a non-invasive spinal cord stimulation in combination with respiratory training. Our aims are: 1) to evaluate the effects of such stimulation applied to the injured spinal cord on pulmonary function and respiratory muscle activity, and 2) to evaluate the effectiveness and therapeutic mechanisms of the spinal cord stimulation combined with respiratory training. Thirty-six individuals with chronic SCI will be recruited and assigned to three groups to receive respiratory training or spinal cord stimulation alone or a combination of them. All participants will be tested before and after cycles of experimental procedures with/or without stimulation. Our hypotheses will be confirmed if the respiratory training combined with spinal cord stimulation results in the most enhanced positive effects.

Conditions

Spinal Cord Injuries; Respiration Disorders

Keywords

Spinal Cord Injury; Respiration; Rehabilitation

Outcome Measures

Primary Outcomes (3)

• Maximum Expiratory Pressure (PEmax).

  Standard Spirometry measurement.

  Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

• Maximum Inspiratory Pressure (PImax).

  Standard Spirometry measurement.

  Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

• Surface electromyography (sEMG) Similarity Index (SI)

  Respiratory multi-muscle activation measures assessed using standard surface electromyography.

  Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

Secondary Outcomes (7)

• Forced Vital Capacity (FVC).

  Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

• Forced Expiratory Volume in 1 second (FEV1).

  Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

• Baroreflex blood pressure sensitivity (BRS).

  Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

• Baroreflex heart rate sensitivity (BRS).

  Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

• Baroreflex blood pressure effectiveness index (BEI).

  Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

Other Outcomes (1)

• The Craig Handicap Assessment & Reporting Technique (CHART) Questionnaire.

  Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.

Study Arms (3)

Training (RT) group

ACTIVE COMPARATOR

80 scTS sessions will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) device applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes. During the intervention, optimally configured scTS will be delivered based on the measures assessed during mapping sessions. The scTS with 5 mA-sub-motor threshold intensity with optimal frequency and pulse width will be delivered using 5 min on and 5 min off stimulation periods during interventional bouts. Every research participant will be slowly acclimated to stimulation. Blood pressure, heart rate, and respiratory rate will be closely monitored throughout stimulation sessions in the Lab by using beat-to-beat blood pressure, and respiratory kinematics monitoring.

Device: Respiratory Training

Spinal Cord Transcutaneous Stimulation (scTS) group

ACTIVE COMPARATOR

Participants will undergo 80 RT sessions using standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504). Participants will be trained at the Frazier Rehab Institute and remotely to complete eighty 45-minute sessions during 16 weeks. The participants will be instructed to perform inspiratory and expiratory efforts against a pressure threshold load. The training will be initiated with a load equal to 20% of their individual Maximum Inspiratory Pressure (PImax) and Maximum Expiratory Pressure (PEmax) values with progressive increases as tolerated up to 60% of their baseline PImax and PEmax measures. The goal will be to reach the 60% load of PImax and PEmax during the last week of each month of the training.

Device: Transcutaneous spinal cord stimulator

Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group

EXPERIMENTAL

Participants will undergo 80 scTS combined with the RT while seated in their own wheelchairs with an approximately 45° head-up tilt. The scTS will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) and Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the RT as described for the Arms 1 and 2.

Device: Transcutaneous spinal cord stimulator; Device: Respiratory Training

Interventions

Transcutaneous spinal cord stimulator DEVICE

Stimulation to the spinal cord will be administered using Neostim/Biostim (Cosyma Inc., Denver CO) device by applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes.

Also known as: Non-invasive spinal cord stimulator

Spinal Cord Transcutaneous Stimulation (scTS) group; Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group

Respiratory Training DEVICE

Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the respiratory training intervention.

Also known as: Respiratory Muscle Training

Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group; Training (RT) group

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;
• no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore or urinary tract infection that might interfere with respiratory training or stimulation;
• no clinically significant depression, psychiatric disorders or ongoing drug abuse;
• non-progressive SCI (no negative change in the neurological level and motor-completeness assessed during screening when compared to the neurological status assessed at 6-mo period after injury or at least 6 months prior to the screening), non-ventilator dependence, motor-complete SCI according to the American Spinal Injury Association Impairment Scale (AIS) grade "A" or "B" above T5 spinal level;
• sustained SCI at least 12 months prior to entering the study;
• compared to the normative values for healthy population, at least 15%-deficit in pulmonary function outcomes (FVC and FEV1) as detected by screening spirometry.

You may not qualify if:

• Participants will be excluded from the study if there is a presence of
• major pulmonary or cardiovascular disease,
• ventilator dependence,
• endocrine disorders,
• malignancy,
• marked obesity,
• deep vein thrombosis,
• HIV/AIDS-related illness,
• secondary hypotension (anemia, hypervolemia, endocrine and neurological diseases),
• major esophageal/gastrointestinal problem or other major medical illness contraindicated for respiratory training or testing.
• During screening, the potential participant will be asked whether she is pregnant or planning to become pregnant during the study period. Pregnant women are excluded from this study, as the risk to the fetus is unknown. No pregnancy test or birth control regimen will be required.

Sponsors & Collaborators

• University of Louisville: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Frazier Rehabilitation and Neuroscience Institute

Louisville, Kentucky, 40202, United States

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries; Respiration Disorders; Respiratory Aspiration

Interventions

Breathing Exercises

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mind-Body Therapies; Complementary Therapies; Therapeutics; Exercise Movement Techniques; Physical Therapy Modalities

Study Officials

• Alexander Ovechkin, MD, PhD

  University of Louisville

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Willhite, MS

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Unidentified data sets will be processed and evaluated by the research staff not directly involved in experimental procedures.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, M.D., Ph.D.

Model Details: Thirty-six SCI participants will be randomly assigned to three groups (n=12 in each group): those who receive RT alone, scTS alone, or a combination of both (scTS+RT). After screening and recruitment, primary and secondary outcome measurements will be obtained in the Lab at the following time points: 1) Pre-intervention, after 30-days without any stimulation and/or intervention, 2) Post mapping, (participants with scTS), 3) Post Session #40 (after 8 weeks of intervention), 4) Post Session #80 (after 16 weeks of intervention), and 5) twice during 16-weeks Follow-up Period. In total, it is anticipated that 6 measurements will be obtained for each participant with scTS and 5 measurements for participants without scTS.

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: August 31, 2023
• Study Start: September 10, 2023
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): April 10, 2030
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)