An Exploratory Clinical Trial of Epidural Spinal Cord Stimulation for Respiratory Recovery in Patients With Brain Injury
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 10
- Locations
- 3
- Primary Endpoint
- Change in Peak Electrical Activity of the Diaphragm From Before to After Spinal Cord Stimulation
Study Overview
Brief Summary
Patients with severe brain injury may develop impaired respiratory drive, diaphragm dysfunction, prolonged mechanical ventilation, and difficulty recovering spontaneous breathing. Epidural spinal cord stimulation may activate preserved spinal respiratory circuits and improve respiratory muscle activity. This prospective, single-center, non-randomized, single-arm exploratory study will enroll 10 patients with stroke or traumatic brain injury who have impaired consciousness and require invasive mechanical ventilation. Participants will undergo epidural spinal cord stimulation in addition to standard clinical care. Diaphragmatic electrical activity, respiratory function, diaphragm ultrasound findings, diaphragm electromyography, duration of mechanical ventilation, pulmonary infection, length of stay, mortality, safety events, and 6-month neurological outcome will be assessed. The study aims to evaluate the safety and preliminary efficacy of epidural spinal cord stimulation for improving respiratory function after brain injury.
Detailed Description
Severe central nervous system injury, including stroke and traumatic brain injury, may impair respiratory drive and disrupt descending pathways between brainstem respiratory centers and spinal respiratory motor networks. This can lead to diaphragm weakness, ineffective cough, secretion retention, prolonged mechanical ventilation, pulmonary infection, and difficulty with ventilator liberation.
Epidural spinal cord stimulation is a neuromodulation approach that may increase the excitability of preserved spinal neural circuits and facilitate respiratory motor output. Preclinical and early clinical evidence suggests that spinal stimulation can enhance respiratory muscle activation and improve ventilatory performance.
This study is a prospective, single-center, interventional, non-randomized, single-arm exploratory trial. Ten adults with imaging-confirmed stroke or traumatic brain injury, a Glasgow Coma Scale score of 3 to 8, and a requirement for invasive mechanical ventilation for at least 24 hours will be enrolled. All participants will undergo epidural spinal cord stimulation in addition to standard treatment. Respiratory physiological measurements will be obtained before and after stimulation. Participants will be followed until hospital discharge and subsequently assessed for survival and neurological outcome at 6 months after injury.
The study will evaluate changes in diaphragmatic electrical activity and other respiratory parameters, as well as pulmonary infection, duration of mechanical ventilation, intensive care unit and hospital length of stay, in-hospital mortality, neurological outcome, and intervention-related adverse events.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18 to 74 years. Body mass index less than 30 kg/m². Imaging-confirmed stroke or traumatic brain injury. Glasgow Coma Scale score of 3 to 8, with relatively stable vital signs. Requirement for invasive mechanical ventilation through an oral or nasal endotracheal tube or tracheostomy for at least 24 hours.
- •Written informed consent provided by the participant's legally authorized representative; if the participant regains decision-making capacity, continued participation will be reconfirmed with the participant.
- •Willingness and ability of the participant or legally authorized representative to comply with the study intervention and follow-up procedures.
Exclusion Criteria
- •Suspected or confirmed infection at the planned electrode implantation site, severe uncontrolled systemic infection, known metal allergy relevant to the implanted device, or uncontrolled intracranial hypertension.
- •Respiratory failure primarily attributable to severe pneumonia, pulmonary contusion, pneumothorax, hemothorax, chronic obstructive pulmonary disease with respiratory failure, severe asthma, or a requirement for home oxygen therapy within the previous 6 months.
- •New York Heart Association class III or IV heart failure or presence of an implanted cardiac pacemaker.
- •Severe hepatic dysfunction, including Child-Pugh class C, severe renal dysfunction with estimated glomerular filtration rate ≤30 mL/min/1.73 m², or dialysis dependence.
- •Status epilepticus or active convulsions. Cervical spinal cord injury, other spinal cord injury, major chest wall deformity, myasthenia, or respiratory dysfunction primarily caused by brainstem injury.
- •Severe psychiatric or pre-existing neurological or cognitive disorders that would interfere with study evaluation or completion, including amyotrophic lateral sclerosis, dementia, Parkinson disease, Huntington disease, or another clinically significant central nervous system disorder unrelated to the index brain injury.
- •Expected survival of 72 hours or less, or a decision to withhold endotracheal intubation, cardiopulmonary resuscitation, or other life-sustaining treatment.
- •Pregnancy or breastfeeding. Any other condition that, in the investigator's judgment, may place the participant at unacceptable risk or interfere with completion of the study.
Arms & Interventions
Epidural Spinal Cord Stimulation
Participants will receive epidural spinal cord stimulation in addition to standard neurosurgical, neurocritical care, mechanical ventilation, airway management, and rehabilitation treatment. Respiratory physiological measurements will be obtained before and after stimulation.
Intervention: Epidural Electrode Implantation (Procedure)
Outcomes
Primary Outcomes
Change in Peak Electrical Activity of the Diaphragm From Before to After Spinal Cord Stimulation
Time Frame: Immediately before stimulation and within 1 hour after stimulation, upto 30 days
Peak electrical activity of the diaphragm will be measured using an electrical activity of the diaphragm catheter. The change from the pre-stimulation value to the post-stimulation value will be reported in microvolts (μV).
Change in Diaphragmatic Electrical Activity Frequency From Before to After Spinal Cord Stimulation
Time Frame: Immediately before stimulation and within 1 hour after stimulation, upto 30 days
The frequency of diaphragmatic electrical activity signals will be measured using an electrical activity of the diaphragm catheter. The change from before to after stimulation will be reported as events per minute.
Secondary Outcomes
- Change in the Frequency of Diaphragmatic Electrical Activity Signals With Peak Amplitude of at Least 3 μV(Immediately before stimulation and within 1 hour after stimulation, upto 30 days)
- Change in the Frequency of Spontaneous Inspiratory Efforts Detected by Diaphragmatic Electrical Activity(Immediately before stimulation and within 1 hour after stimulation, upto 30 days)
- ICU Length of Stay(From enrollment through intensive care unit discharge, up to 6 months)
- Spontaneous Respiratory Rate(Immediately before stimulation and within 1 hour after stimulation, upto 30 days)
- Change in Tidal Volume From Before to After Spinal Cord Stimulation(Immediately before stimulation and within 1 hour after stimulation, upto 30 days)
- Diaphragmatic Excursion(Immediately before stimulation and within 1 hour after stimulation upto 30 days)
- Diaphragm Thickening Fraction(Immediately before stimulation and within 1 hour after stimulation upto 30 days)
- Duration of Mechanical Ventilation(From enrollment through hospital discharge, up to 6 months)
- Hospital Length of Stay(From hospital admission through hospital discharge, up to 6 months)
- In-Hospital Mortality(From enrollment through hospital discharge, up to 6 months)
- Adverse Events Related to the Procedure or Device(From implantation through the 6-month follow-up)
Investigators
Fei Peng
Sub-Investigator
Zhongda Hospital