Clinical trial NCT06019949: Spinal Cord Stimulation for Respiratory Rehabilitation in Patients With Chronic Spinal Cord Injury
Official title: Neuromodulatory Rehabilitation for Respiratory Motor Function in Individuals With Chronic Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Respiration Disorders
Keywords: Spinal Cord Injury
Respiration
Rehabilitation
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-08-31
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: This is a respiratory rehabilitation-based clinical study consisting of physiologically and functionally relevant mapping of respiratory function that enhances our knowledge of neurophysiological modulation evoked by non-invasive spinal cord Transcutaneous Stimulation (scTS) and contributes to the development of the next generation of rehabilitative approaches. Following the screening process and recruiting, the research subjects will undergo the following procedures: Subjects (total n=36) will be randomly assigned to three groups and will undergo baseline assessments; evaluations before and after 80 sessions of specific intervention (Respiratory Training /RT/ alone, scTS alone, or RT in combination with scTS); and during 16 week-long follow up period.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

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.

Primary outcomes:
measure: Maximum Expiratory Pressure (PEmax).
timeFrame: 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.
measure: Maximum Inspiratory Pressure (PImax).
timeFrame: 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.
measure: Surface electromyography (sEMG) Similarity Index (SI)
timeFrame: 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:
measure: Forced Vital Capacity (FVC).
timeFrame: 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.
measure: Forced Expiratory Volume in 1 second (FEV1).
timeFrame: 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.
measure: Baroreflex blood pressure sensitivity (BRS).
timeFrame: 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.
measure: Baroreflex heart rate sensitivity (BRS).
timeFrame: 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.
measure: Baroreflex blood pressure effectiveness index (BEI).
timeFrame: 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.
measure: Baroreflex heart rate effectiveness index (BEI).
timeFrame: 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.
measure: Spinal Cord Independence Measure (SCIM, Version III).
timeFrame: 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:
measure: The Craig Handicap Assessment & Reporting Technique (CHART) Questionnaire.
timeFrame: 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.
Locations:
city: Louisville
country: United States
facility: Frazier Rehabilitation and Neuroscience Institute
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Alexander Ovechkin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: