Spinal Cord Injury Cervical, Respiratory Failure
Conditions
Keywords
respiratory failure, spinal cord injury, epidural spinal cord electrical stimulation, diaphragm electrical activity
Brief summary
This multicenter, single-arm exploratory IIT evaluates epidural spinal cord electrical stimulation (ESCES) in 20 adults with C1-C5 SCI and respiratory failure. Participants receive ESCES plus standard care; electrodes are implanted at C3-C5 with daily individualized stimulation. Primary outcomes: Edi peak, change of Edi peak and frequency. Secondary: tidal volume, maximal inspiratory pressure, NVE, NME, diaphragm ultrasound, cough strength, 90-day ventilator-free days, ICU stay, and survival. This is the first systematic ESCES study for SCI-related respiratory failure, aiming to provide preliminary safety/efficacy data for future RCTs.
Detailed description
This is a multicenter, prospective, single-arm, exploratory investigator-initiated trial (IIT) conducted at Zhongda Hospital, Southeast University and the First Affiliated Hospital of Nanjing Medical University. The study aims to evaluate the safety and efficacy of epidural spinal cord electrical stimulation (ESCES) in patients with spinal cord injury (SCI) complicated by respiratory failure. A total of 20 adult patients (aged 18-75 years) with C1-C5 level SCI for at least 2 weeks and respiratory failure requiring mechanical ventilation or presenting with hypoxemia/hypercapnia will be enrolled. Participants will receive standard conventional treatment plus ESCES. Electrodes will be surgically implanted at the C3-C5 epidural space, and stimulation will be delivered daily with individualized parameter titration based on patient tolerance. The primary outcomes are Edi peak, change of Edi peak and frequency. Secondary outcomes include tidal volume, diaphragmatic ultrasound parameters, cough strength, 90-day ventilator-free days, ICU length of stay, and survival at 90 and 180 days. The observation period is defined as the period from enrollment until 1 month after enrollment or until successful weaning from mechanical ventilation, ICU discharge, removal of the epidural stimulation electrode, withdrawal from the study, or death, whichever occurs first. This study is the first systematic exploration of ESCES for respiratory function recovery in SCI patients with respiratory failure, and may provide a novel therapeutic strategy for this population. The trial is expected to run for approximately 30 months. Participation is voluntary, and participants may withdraw at any time without affecting their subsequent care.
Interventions
①Epidural electrode implantation Under general anesthesia, two epidural electrodes will be implanted through a posterior cervical approach and positioned over the dorsal epidural space at the C3-C5 spinal levels. An implantable pulse generator will be placed in the lateral chest wall. ②.Epidural Spinal Cord Stimulation ESCS will begin on postoperative day 2. Initial stimulation parameters will include: * Pulse width: 200 μs (maximum 500μs) * Frequency: initially 10 Hz, gradually increased up to 60 Hz (maximum 300 Hz) according to tolerance * Current intensity: initially 1 mA, increased in 0.5 mA increments to the maximum tolerated intensity (up to 20 mA) Stimulation will be delivered daily. Stimulation parameters will be recorded throughout the study, and settings may be adjusted to minimize discomfort. Additional supportive care will be provided as clinically indicated.
Sponsors
Zhongda Hospital
The First Affiliated Hospital with Nanjing Medical University
Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 75 years, with BMI \<30 kg/m². 2. Cervical SCI involving levels C1-C5 for at least 2 weeks. 3. Respiratory failure defined by one or more of the following: * Peripheral oxygen saturation \<90% on room air; * Arterial oxygen tension (PaO₂) \<60 mmHg; * Respiratory acidosis (PaCO₂ \>45 mmHg with pH \<7.35); * Requirement for mechanical ventilation. 4. Maximum inspiratory pressure (MIP) \>-15 cmH₂O. 5. Judged by the treating physician to be unable to tolerate continuous ventilator weaning for ≥48 hours due to SCI. 6. Written informed consent provided by the participant or legally authorized representative.
Exclusion criteria
1. Active infection at the planned electrode implantation site, severe systemic infection, or existing implanted neurostimulation devices. 2. Respiratory failure primarily caused by severe pneumonia, pulmonary contusion, pneumothorax, hemothorax, chronic obstructive pulmonary disease, or requirement for home oxygen therapy within the previous 6 months. 3. New York Heart Association (NYHA) class III or IV heart failure or implanted cardiac pacemaker. 4. Severe hepatic or renal dysfunction (Child-Pugh class C liver disease or estimated glomerular filtration rate ≤30 mL/min/1.73 m²) or dialysis dependence. 5. Generalized seizures, traumatic brain injury, intracranial hypertension, intracranial aneurysm with Glasgow Coma Scale score ≤12, or neuromuscular disorders affecting respiratory function. 6. Expected survival \<72 hours or refusal of life-sustaining treatment. 7. Pregnancy or breastfeeding. 8. Any other condition considered by the investigator to make study participation inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | From epidural electrode implantation through Day 30. | Incidence of Adverse Events and Serious Adverse Events Related to Epidural Spinal Cord Stimulation; Safety will be assessed by the occurrence of adverse events (AEs) and serious adverse events (SAEs) considered possibly, probably, or definitely related to epidural electrode implantation, the stimulation device, or epidural spinal cord stimulation. |
| Diaphragmatic function | From epidural electrode implantation through Day 30. | Peak electrical activity of the diaphragm (Edi peak): Peak electrical activity of the diaphragm measured using an electrical activity of the diaphragm (Edi) catheter. Values are reported in microvolts (μV). Diaphragmatic electrical activity frequency (Edi frequency): Diaphragmatic electrical activity frequency measured using an electrical activity of the diaphragm (Edi) catheter. Values are reported as breaths per minute (breaths/min). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital length of stay | up to 90 days | Total length of hospitalization, reported in days. |
| Maximum tidal volume | up to 1 month | Maximum tidal volume measured by the mechanical ventilator during pressure support ventilation. Values are reported in milliliters (mL). |
| Change in peak electrical activity of the diaphragm (Edi peak) from baseline | up to 1 month | Change in peak electrical activity of the diaphragm (Edi peak) from baseline, Change from baseline in peak electrical activity of the diaphragm measured using an Edi catheter. Values are reported in microvolts (μV). |
| Frequency of spontaneous breaths triggered by diaphragmatic electrical activity | up to 1 month | The frequency of spontaneous breaths triggered by the patient's diaphragmatic electrical activity and detected using an Edi catheter. Breaths triggered solely by the mechanical ventilator without a corresponding Edi signal are excluded. Values are reported as breaths per minute (breaths/min). |
| Neuroventilatory efficiency (NVE) | up to 1 month | Neuroventilatory efficiency of the diaphragm, calculated as the ratio of tidal volume to peak electrical activity of the diaphragm (VT/Edi). NVE reflects the tidal volume generated per unit of neural respiratory drive and represents the integrated performance of diaphragm function and respiratory load. Values are reported in mL/μV. |
| Neuro-mechanical efficiency (NME) | up to 1 month | Neuro-mechanical efficiency of the diaphragm, calculated as the ratio of the change in airway pressure during an end-inspiratory occlusion maneuver to the corresponding peak electrical activity of the diaphragm (ΔPaw/Edi). NME reflects the pressure-generating capacity (contractile efficiency) of the diaphragm per unit of neural respiratory drive. Values are reported in cmH₂O/μV. |
| Airway occlusion pressure at 100 milliseconds (P0.1) | up to 1 month | Airway occlusion pressure measured 100 milliseconds after the onset of inspiratory effort using the ventilator monitoring system. Values are reported in cmH₂O. |
| Airway occlusion pressure during end-expiratory occlusion (Pocc) | up to 1 month | Airway occlusion pressure measured during an end-expiratory occlusion maneuver using the ventilator monitoring system. Values are reported in cmH₂O. |
| Maximum inspiratory pressure (MIP) | up to 1 month | Maximum inspiratory pressure (MIP) measured using an inspiratory pressure measurement maneuver. MIP represents the maximum negative airway pressure generated during a maximal inspiratory effort against an occluded airway and reflects global inspiratory muscle strength. Values are reported in cmH₂O. |
| Diaphragm thickness | up to 1 month | Diaphragm thickness measured by diaphragm ultrasonography. Values are reported in millimeters (mm). |
| Diaphragm thickening fraction | up to 1 month | Diaphragm thickening fraction measured by diaphragm ultrasonography. Values are reported as percentages (%). |
| Diaphragmatic excursion | up to 1 month | Diaphragmatic excursion measured by diaphragm ultrasonography. Values are reported in millimeters (mm). |
| Acute Physiology and Chronic Health Evaluation II (APACHE II) score | up to 1 month | Disease severity assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Scores range from 0 to 71, with higher scores indicating greater disease severity and a higher risk of mortality. |
| Sequential Organ Failure Assessment (SOFA) score | up to 1 month | Organ dysfunction assessed using the Sequential Organ Failure Assessment (SOFA) score. Scores range from 0 to 24, with higher scores indicating more severe organ dysfunction and worse clinical status. |
| Ventilator-free days within 90 days | Within 90 days after enrollment. | Number of days alive and free from invasive mechanical ventilation during the first 90 days after enrollment. |
| Daily time off mechanical ventilation (hours/day) | up to 1 month | Total duration per day during which the patient breathes spontaneously without mechanical ventilatory support. Values are reported in hours per day (hours/day). |
| Intensive care unit (ICU) length of stay | up to 90 days | Length of stay in the intensive care unit, reported in days. |
Countries
China
Contacts
CONTACTFei Peng, Dr. PhD.
CONTACTJianfeng Xie, Dr. PhD.
Outcome results
None listed