Air Mixture + Electrical Stimulation for Spinal Cord Injury

(AIHH+tSCS Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Thomas Jefferson University

Disqualifiers: Cardiopulmonary disease, Ventilator support, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to determine whether people with paralysis due to a spinal cord injury can benefit from breathing short intermittent bouts of air with low oxygen (O2) combined with slightly higher levels of carbon dioxide (CO2), interspaced by breathing room air. The technical name for this therapeutic air mixture is 'acute intermittent hypercapnic-hypoxia,' abbreviated as AIHH. Following exposure to the gas mixture, participants will receive non-invasive electrical stimulation to the spinal cord paired with specific and targeted exercise training. The main question this trial aims to answer is: Can the therapeutic application of AIHH, combined with non-invasive electrical stimulation to the spinal cord plus exercise training, increase the strength of muscles involved in breathing and hand function in people with paralysis due to a spinal cord injury? Participants will be asked to attend a minimum of five study visits, each separated by at least a week. During these visits, participants will be required to: * Answer basic questions about their health * Receive exposure to the therapeutic air mixture (AIHH) * Undergo non-invasive spinal electrical stimulation * Complete functional breathing and arm strength testing * Undergo a single blood draw * Provide a saliva sample Researchers will compare the results of individuals without a spinal cord injury to those of individuals with a spinal cord injury to determine if the effects are similar.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment for spinal cord injury?

Research shows that transcutaneous spinal cord stimulation (tSCS) can enhance voluntary movement, muscle strength, and function in people with chronic spinal cord injury. Additionally, high-frequency spinal cord stimulation (HF-SCS) has been shown to activate inspiratory muscles, which may help with breathing in patients with spinal cord injuries.

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Is transcutaneous spinal cord stimulation (tSCS) safe for humans?

Transcutaneous spinal cord stimulation (tSCS) is considered a safe, non-invasive technique for modulating spinal cord activity, as indicated by studies evaluating its effects on spinal cord excitability and motor responses in individuals with spinal cord injury.

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How does the Air Mixture + Electrical Stimulation treatment for spinal cord injury differ from other treatments?

This treatment is unique because it combines Acute Intermittent Hypercapnic Hypoxia (AIHH), which involves controlled exposure to low oxygen levels, with Transcutaneous Spinal Cord Stimulation (tSCS), a non-invasive method that uses electrical currents to stimulate the spinal cord. This combination aims to enhance recovery by promoting neural activity and improving motor function, which is different from traditional treatments that may not use both hypoxia and electrical stimulation together.

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Eligibility Criteria

Adults aged 18-65 with non-progressive spinal cord injuries from C2-T1, classified as AIS B, C, or D. They should have impaired breathing strength and be able to engage in therapy programs. Must be at least a year post-injury, capable of consent, have caregiver support, and willing to be recorded.

Inclusion Criteria

Has adequate caregiver support to facilitate participation in study

Willingness to undergo non-deidentifiable audio and/or visual recording

You have more than 20% difficulty in breathing compared to normal values.

Exclusion Criteria

I have heart or lung conditions that are not well-managed.

Most of my muscles do not respond due to nerve damage.

I do not have any major health issues that could affect the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Clinical Assessment

Comprehensive clinical assessments to characterize each individual's clinical presentation and SCI, and to determine initial status to monitor safety and responses to study procedures.

1 visit

1 visit (in-person)

Treatment

Participants receive AIHH or Sham exposure followed by tSCS paired with respiratory and upper extremity strength training.

5 weeks

5 visits (in-person), each separated by at least a week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-testing of neurophysiology and functional assessments.

1 week

1 visit (in-person)

Participant Groups

The trial tests if a mix of low oxygen and high carbon dioxide air (AIHH), along with electrical stimulation and exercise training can improve breathing and hand function in those paralyzed due to spinal injury. It involves health questions, AIHH exposure, stimulation sessions, strength testing, blood draw and saliva sample.

Group I: SHAM AIHH + tSCS-paired Strength Training Experimental Treatment 2 Interventions

Participants will receive exposure to SHAM AIHH followed by transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Group II: AIHH + SHAM tSCS-paired Strength Training Experimental Treatment 2 Interventions

Participants will receive exposure to AIHH followed by SHAM transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Group III: AIHH + tSCS-paired Strength Training Active Control 2 Interventions

Participants will receive exposure to AIHH followed by transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Group IV: SHAM AIHH + SHAM tSCS-paired Strength Training Placebo Group 2 Interventions

Participants will receive exposure to SHAM AIHH followed by SHAM transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Thomas Jefferson University Philadelphia, PA

Who Is Running the Clinical Trial?

Thomas Jefferson University Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Model-Based Optimization of Spinal Cord Stimulation for Inspiratory Muscle Activation. [2022] High-frequency spinal cord stimulation (HF-SCS) is a potential method to provide natural and effective inspiratory muscle pacing in patients with ventilator-dependent spinal cord injuries. Experimental data have demonstrated that HF-SCS elicits physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways. However, the activation thresholds, extent of activation, and optimal electrode configurations (i.e., lead separation, contact spacing, and contact length) to activate these neural elements remain unknown. Therefore, the goal of this study was to use a computational modeling approach to investigate the direct effects of HF-SCS on the spinal cord and to optimize electrode design and stimulation parameters.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. [2022] To evaluate the impact of using transcutaneous electrical spinal cord stimulation (TSCS) on upper and lower extremity function in individuals with chronic spinal cord injury (SCI).

3. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation and Motor Rehabilitation in Spinal Cord Injury: A Systematic Review. [2021] Background. Epidural spinal electrical stimulation at the lumbar spinal level evokes rhythmic muscle activation of lower-limb antagonists, attributed to the central pattern generator. However, the efficacy of noninvasive spinal stimulation for the activation of lower-limb muscles is not yet clear. This review aimed to analyze the feasibility and efficacy of noninvasive transcutaneous spinal cord stimulation (tSCS) on motor function in individuals with spinal cord injury. Methods. A search for tSCS studies was made of the following databases: PubMed; Cochrane Registry; and Physiotherapy Evidence Database (PEDro). In addition, an inverse manual search of the references cited by the identified articles was carried out. The keywords transcutaneous, non-invasive, electrical stimulation, spinal cord stimulation [Mesh term], and spinal cord injury were used. Results. A total of 352 articles were initially screened, of which 13 studies met the inclusion criteria for systematic review. The total participant sample comprised 55 persons with spinal cord injury. All studies with tSCS provided evidence of induced muscle activation in the lower and upper limbs, and applied stimulation at the level of the T11-T12 and C4-C7 interspinous space, respectively. All studies reported an increase in motor response measured by recording surface electromyography, voluntary movement, muscle strength, or function. Conclusions. Although this review highlights tSCS as a feasible therapeutic neuromodulatory strategy to enhance voluntary movement, muscle strength, and function in patients with chronic spinal cord injury, the clinical impact and efficacy of electrode location and current intensity need to be characterized in statistically powered and controlled clinical trials.

4. Netherlands pubmed.ncbi.nlm.nih.gov

Intercostal muscle pacing with high frequency spinal cord stimulation in dogs. [2021] High frequency spinal cord stimulation (HF-SCS) is a novel and more physiologic method of inspiratory muscle activation which involves stimulation of spinal cord pathways. In the present study, we determined if activation of the inspiratory intercostal muscles alone by this technique could be utilized to maintain artificial ventilation. In 7 anesthetized dogs, following C2 spinal cord section and bilateral phrenicotomy, trains of electrical stimulation (12 times/min) were applied at the T2 level. Eucapnea was maintained during an initial 5.5h period of continuous stimulation. During a subsequent 0.5h period, stimulus parameters were increased to induce hyperventilation resulting in a sustained fall in end-tidal P(CO(2)) to 29.3 + or - 0.4 mmHg. Single motor unit peak firing frequencies of the intercostal muscles during HF-SCS were similar to those occurring during spontaneous breathing. This technique holds promise as a method to restore ventilation in ventilator-dependent tetraplegics who do not have adequate phrenic nerve function for diaphragm pacing.

5. England pubmed.ncbi.nlm.nih.gov

High-frequency spinal cord stimulation as rescue therapy for chronic pain patients with failure of conventional spinal cord stimulation. [2021] This study aims to evaluate the efficacy of 10-kHz high-frequency (HF10) devices as a rescue treatment in patients with failure of conventional spinal cord stimulation (SCS) therapy for chronic pain without the need to change the spinal hardware.

6. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. [2022] Transcutaneous spinal cord stimulation (tSCS) is a non-invasive modality in which electrodes can stimulate spinal circuitries and facilitate a motor response. This review aimed to evaluate the methodology of studies using tSCS to generate motor activity in persons with spinal cord injury (SCI) and to appraise the quality of included trials.

7. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Spinal direct current stimulation with locomotor training in chronic spinal cord injury. [2021] Transcutaneous spinal direct current stimulation (tsDCS) is a non-invasive method of stimulating spinal circuits that can modulate and induce changes in corticospinal excitability (CE) in incomplete spinal cord injury (SCI). A double-blinded sham controlled study of 2 male patients (A and B) with SCI was carried out. Patient A received sham and cathodal tsDCS, while Patient B received sham and anodal tsDCS. Four baselines were recorded prior to each arm of stimulation. Outcomes were then measured post each arm of stimulation; 10-meter walk test, modified ashworth scale, berg balance scale, manual muscle testing, and spinal cord independence measure-III. Transcranial magnetic stimulation, assessed motor evoked potentials. Cathodal tsDCS increased the scores in few of the outcome measures and decreased others. Anodal stimulation increased scores in all measures. Motor evoked potentials increased in post-cathode and deteriorated in post-anode. In conclusion, tsDCS modulated gait parameters, spasticity, and CE in incomplete SCI.

8. United States pubmed.ncbi.nlm.nih.gov

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition. [2022] Transcutaneous spinal direct current stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We assessed changes in intracortical excitability following tsDCS by evaluating changes in cortical silent period (cSP), paired-pulse short intracortical inhibition (SICI), and intracortical facilitation (ICF).

9. England pubmed.ncbi.nlm.nih.gov

Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study. [2022] Objective.Transcutaneous spinal cord stimulation (TSS) has been shown to be a promising non-invasive alternative to epidural spinal cord stimulation for improving outcomes of people with spinal cord injury (SCI). However, studies on the effects of TSS on cortical activation are limited. Our objectives were to evaluate the spatiotemporal effects of TSS on brain activity, and determine changes in functional connectivity under several different stimulation conditions. As a control, we also assessed the effects of functional electrical stimulation (FES) on cortical activity.Approach. Non-invasive scalp electroencephalography (EEG) was recorded during TSS or FES while five neurologically intact participants performed one of three lower-limb tasks while in the supine position: (1) A no contraction control task, (2) a rhythmic contraction task, or (3) a tonic contraction task. After EEG denoising and segmentation, independent components (ICs) were clustered across subjects to characterize sensorimotor networks in the time and frequency domains. ICs of the event related potentials (ERPs) were calculated for each cluster and condition. Next, a Generalized Partial Directed Coherence (gPDC) analysis was performed on each cluster to compare the functional connectivity between conditions and tasks.Main results. IC analysis of EEG during TSS resulted in three clusters identified at Brodmann areas (BA) 9, BA 6, and BA 4, which are areas associated with working memory, planning, and movement control. Lastly, we found significant (p < 0.05, adjusted for multiple comparisons) increases and decreases in functional connectivity of clusters during TSS, but not during FES when compared to the no stimulation conditions.Significance.The findings from this study provide evidence of how TSS recruits cortical networks during tonic and rhythmic lower limb movements. These results have implications for the development of spinal cord-based computer interfaces, and the design of neural stimulation devices for the treatment of pain and sensorimotor deficit.

10. United States pubmed.ncbi.nlm.nih.gov

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. [2021] An increasing number of studies supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes functional recovery in humans with spinal cord injury (SCI). However, the neural mechanisms contributing to these effects remain poorly understood. Here we examined motor-evoked potentials in arm muscles elicited by cortical and subcortical stimulation of corticospinal axons before and after 20 min of TESS (30 Hz pulses with a 5 kHz carrier frequency) and sham-TESS applied between C5 and C6 spinous processes in males and females with and without chronic incomplete cervical SCI. The amplitude of subcortical, but not cortical, motor-evoked potentials increased in proximal and distal arm muscles for 75 min after TESS, but not sham-TESS, in control subjects and SCI participants, suggesting a subcortical origin for these effects. Intracortical inhibition, elicited by paired stimuli, increased after TESS in both groups. When TESS was applied without the 5 kHz carrier frequency both subcortical and cortical motor-evoked potentials were facilitated without changing intracortical inhibition, suggesting that the 5 kHz carrier frequency contributed to the cortical inhibitory effects. Hand and arm function improved largely when TESS was used with, compared with without, the 5 kHz carrier frequency. These novel observations demonstrate that TESS influences cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. We hypothesized that these parallel effects contribute to further the recovery of limb function following SCI.SIGNIFICANCE STATEMENT Accumulating evidence supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes recovery of function in humans with spinal cord injury (SCI). Here, we show that a single session of TESS over the cervical spinal cord in individuals with incomplete chronic cervical SCI influenced in parallel the excitability cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. Importantly, these parallel physiological effects had an impact on the magnitude of improvements in voluntary motor output.