Clinical trial NCT06847295: Epidural Electrical Stimulation to Restore Standing and Walking in Patients With Chronic Paralysis Due to Spinal Cord Injury: A Study on Motor Recovery, Spasticity Reduction, and Quality of Life Improvement Through Neuromodulation and Intensive Rehabilitation
Official title: Epidural Electrical Stimulation for Motor and Functional Recovery in Patients With Chronic Paralysis Due to Spinal Cord Injury: A Prospective Study Evaluating Gait Restoration, Spasticity Reduction, Pain Management, and Quality of Life Improvements Through Neuromodulation and Intensive Rehabilitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries (SCI)
Paralysis, Lower Limbs
Keywords: Spinal Cord Injury
Spinal Cord Stimulation
Epidural Stimulation
Neuroplasticity
Rehabilitation
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2025-02-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Spinal cord injury (SCI) is a major cause of morbidity and disability worldwide, significantly impacting patients' quality of life and functional independence. Despite advances in rehabilitation therapies, many individuals with SCI remain unable to stand or walk. Epidural electrical stimulation (EES) has emerged as a promising neuromodulation therapy to restore motor function in individuals with chronic paralysis.

This prospective clinical study aims to evaluate the efficacy and safety of EES in patients with chronic SCI who have lost the ability to stand or walk. The primary objective is to assess late-stage gait recovery following the implantation of an epidural spinal cord stimulator, using validated clinical scales such as the Fugl-Meyer Assessment - Lower Extremity (FMA-LE) and BMCA VRI.

Secondary objectives include evaluating:

The ability to stand independently (measured by the Berg Balance Scale). Improvements in walking capacity, with or without assistance. Changes in spasticity induced by EES (Modified Ashworth Scale). Reduction in pain perception (DN4, Brief Pain Inventory \[BPI\], Pain Disability Index \[PDI\]).

Improvements in neurogenic bladder and bowel dysfunction (NBSS and NBDS). Enhancements in quality of life (SCI-QOL, WHOQOL-BREF) and mood (Beck Depression Inventory \[BDI\]).

The study will recruit 10 adult patients (ages 18-50) with chronic, stable SCI (≥6 months post-injury) classified as ASIA A or B, with lesions between C7 and T10 and intact segmental reflexes below the injury level. Participants will undergo an intensive 3-month pre-implant rehabilitation program to maximize their baseline motor potential.

Following this period, eligible patients will receive surgical implantation of an epidural spinal cord stimulator (Medtronic Specify 5-6-5 paddle lead and Intellis pulse generator). After a 1-month post-surgical recovery period, patients will engage in a 12-month intensive rehabilitation protocol (5 supervised sessions per week), with the stimulator activated to facilitate motor recovery.

Patients will be assessed monthly through clinical evaluations and surface electromyography (EMG) to measure motor control improvements. Outcomes will be compared before and after EES implantation to determine the effectiveness of the intervention.

This study seeks to provide further evidence on the potential of epidural electrical stimulation in restoring standing and walking abilities in individuals with SCI. If successful, it could contribute to expanding treatment options for patients with chronic paralysis.

Detailed description: Introduction and Rationale:

Spinal cord injury (SCI) is a major cause of long-term disability and diminished quality of life, with current rehabilitation methods often falling short of restoring independent mobility. Emerging evidence suggests that neuromodulation, particularly Epidural Electrical Stimulation (EES), can facilitate the reactivation of dormant spinal networks, thereby promoting motor recovery. Preclinical studies and initial clinical reports have demonstrated that EES can enhance neuroplasticity and improve gait function in patients with chronic paralysis. This study is designed to build on these findings by evaluating the efficacy and safety of EES in a cohort of patients with chronic, stable SCI who have lost the ability to stand or walk.

Study Objectives:

The primary objective of this prospective study is to assess late-stage gait recovery after the surgical implantation of an epidural spinal cord stimulator. Secondary objectives include improvements in standing balance, walking capacity (with or without assistance), reduction in spasticity, pain management, and enhancements in neurogenic bladder and bowel function, as well as overall quality of life and mood. This extended description outlines the technical aspects of the study design, surgical procedure, rehabilitation protocols, and neurophysiological assessments.

Study Design and Overall Methodology:

This is a single-arm, prospective clinical study designed to follow each patient as their own control by comparing pre-operative and post-operative functional status. The study will enroll 10 adult patients with chronic SCI (≥6 months post-injury) classified as ASIA A or B, with lesions located between C7 and T10 and preserved segmental reflexes below the level of injury. Prior to surgical intervention, participants will undergo a 3-month intensive rehabilitation program aimed at maximizing their baseline motor function. This phase includes five supervised physiotherapy sessions per week, during which comprehensive clinical assessments, video documentation, and surface electromyography (EMG) recordings are collected.

Surgical Procedure and Device Implantation:

Following the pre-operative rehabilitation phase, patients will undergo a surgical procedure for the implantation of an epidural spinal cord stimulator. The procedure is performed in a sterile operating room at the Hospital das Clínicas, Faculty of Medicine, University of São Paulo. Key technical details of the procedure include:

Patient Positioning and Preparation: Patients are positioned prone, and the operative site is marked using fluoroscopic guidance. Standard aseptic protocols are followed.

Incision and Exposure: A midline skin incision, approximately 5-8 cm in length, is made between the T12 and L2 vertebral levels. Dissection is carried out through the subcutaneous tissue and paravertebral muscles.

Creation of an Interlaminar Window: An interlaminar window is created at the L1/L2 level to provide access to the epidural space.

Electrode Implantation: A paddle lead (Medtronic Specify 5-6-5, featuring 16 channels arranged in three rows) is implanted in the lumbar epidural space, targeting the region between T11 and L1 to cover the dermatomes from L1 to S2. Intraoperative neurophysiological monitoring using EMG is employed to verify the precise placement of the electrode.

Pulse Generator Placement: A subcutaneous pocket is created in the right flank for the implantation of the pulse generator (Medtronic Intellis). The device is tested intraoperatively to ensure optimal performance and appropriate neuromodulatory response.

Post-Operative and Rehabilitation Protocol:

After a post-surgical recovery period of one month-allowing for wound healing and initial device programming-patients will enter the post-implant rehabilitation phase. This phase consists of a 12-month period during which patients participate in intensive, supervised physiotherapy sessions (five sessions per week). During these sessions:

Activation of EES: The epidural electrical stimulation is activated to facilitate motor recovery. Stimulation parameters (e.g., intensity, frequency, pulse width) are individually adjusted based on patient response and neurophysiological feedback.

Ongoing Evaluations: Regular assessments are conducted monthly using both clinical scales and surface EMG recordings. These evaluations monitor improvements in gait, balance, and overall motor control. Video recordings are also made to document functional performance.

Neurophysiological and Technical Assessments:

A critical component of the study is the use of surface electromyography (EMG) to provide quantitative measures of muscle activity and neuromuscular coordination. Technical details include:

Equipment: A wireless 8-channel EMG system (Trigno Avanti Research+, Delsys) will be used for data acquisition.

Muscle Groups Monitored: EMG electrodes will be placed on key muscles involved in gait and posture, including the iliopsoas, vastus lateralis, rectus femoris, tibialis anterior, semitendinosus, gastrocnemius, soleus, extensor hallucis longus, biceps femoris, and gluteus maximus.

Data Acquisition: EMG signals are filtered (band-pass range between 30 and 500 Hz) and digitized at a sampling rate of 2 kHz. Data analysis is performed offline using Matlab (R2019a) to correlate neuromuscular responses with clinical outcomes.

Safety and Risk Management:

The safety profile of EES is well established in the literature. However, potential risks include surgical complications such as infection, hematoma, device migration, or transient worsening of neurological status. To mitigate these risks, the study incorporates:

Intraoperative Monitoring: Continuous EMG monitoring during electrode implantation to ensure proper placement.

Post-Operative Care: Close monitoring during the recovery phase and strict adherence to infection control protocols.

Adverse Event Reporting: All complications will be recorded and managed according to established clinical guidelines.

Study Timeline and Follow-Up:

The overall study duration for each participant is approximately 16 months, which includes:

A 3-month pre-operative rehabilitation phase. Surgical implantation of the EES device. A 1-month post-operative recovery period. A 12-month post-implant rehabilitation and evaluation phase. Regular follow-up visits will be scheduled for clinical assessments, EMG recordings, and video documentation to continuously monitor progress and adjust therapy as needed.

Ethical Considerations and Regulatory Compliance:

The study protocol has been approved by the Ethics Committee for Research Project Analysis at Hospital das Clínicas, Faculty of Medicine, University of São Paulo (HC-FMUSP). All participants will provide written informed consent prior to enrollment. Given the significant unmet need for effective treatments in chronic SCI and the promising results of neuromodulation in preliminary studies, the design of this study-with patients serving as their own control-is considered ethically justifiable. The study complies with institutional, national, and international regulatory guidelines regarding clinical research and device implantation.

Significance and Expected Impact:

This study aims to provide robust evidence on the efficacy of epidural electrical stimulation in promoting functional motor recovery in patients with chronic spinal cord injury. By combining advanced neuromodulatory techniques with intensive rehabilitation, the study seeks to demonstrate improvements in gait, balance, and overall quality of life. Successful outcomes could lead to broader clinical application of EES and represent a significant advancement in the management of chronic SCI.

Conclusion:

The proposed study is a comprehensive investigation into the application of epidural electrical stimulation as a therapeutic intervention for chronic spinal cord injury. Through meticulous surgical technique, rigorous rehabilitation protocols, and detailed neurophysiological assessments, the study is designed to explore the mechanisms of neuromodulation and validate the clinical benefits of EES. The integration of technical and clinical data is expected to contribute valuable insights that may ultimately transform the treatment landscape for patients with severe, chronic paralysis.

Eligibility criteria: Inclusion Criteria:

* Adult patients aged 18 to 50 years.
* Stable spinal cord injury (SCI) at least 6 months post-injury.
* Classified as ASIA A or B with inability to stand or walk.
* Injury located between C7 and T10.
* Intact segmental reflexes below the level of injury.
* Ability to understand and sign the informed consent form.
* Willingness and capability to attend daily physiotherapy sessions.
* Clinically stable overall health as determined by the investigators.

Exclusion Criteria:

* Current use of electronic devices such as baclofen pumps or cardiac pacemakers.
* Presence of comorbidities that increase surgical risk (e.g., anticoagulation therapy, cardiopulmonary issues).
* Locomotor deformities or additional neurological disorders that may compromise evaluation.
* Significant dysautonomia or history of stroke or myocardial infarction associated with autonomic dysreflexia.
* MRI evidence of complete spinal cord transection, significant spinal atrophy, or significant syringomyelia.
* Uncontrolled pain, severe spasticity, or other conditions that hinder rehabilitation participation.
* Suspected abuse of opioids, alcohol, or other illegal substances.
* Estimated life expectancy of less than 2 years due to severe concomitant malignant or clinical conditions.
* Clinically significant mental health disorders.
* Botulinum toxin injections received in the past 6 months.
* Presence of voluntary movements during EMG testing in the lower extremities.
* Unhealed vertebral fractures.
* Presence of pressure ulcers.
* Active infection.
* Pregnancy.

Primary outcomes:
measure: Late-Stage Gait Recovery Assessed by the Fugl-Meyer Assessment for Lower Extremities
timeFrame: Baseline and monthly evaluations over 12 months following epidural stimulator implantation
measure: Late-Stage Gait Recovery Assessed by the Brain Motor Control Assessment - Voluntary Response Index
timeFrame: Baseline and monthly evaluations over 12 months following epidural stimulator implantation
Secondary outcomes:
measure: Balance Assessed by the Berg Balance Scale
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Walking Ability
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Spasticity Assessed by the Modified Ashworth Scale
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Pain Perception Assessed by the Douleur Neuropathique 4 Questions
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Pain Severity Assessed by the Brief Pain Inventory
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Pain-Related Disability Assessed by the Pain Disability Index
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Neurogenic Bladder Function Assessed by the Neurogenic Bladder Symptom Score
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Neurogenic Bowel Function Assessed by the Neurogenic Bowel Dysfunction Score
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Quality of Life Assessed by the World Health Organization Quality of Life - Brief Version
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
measure: Mood Assessed by the Beck Depression Inventory
timeFrame: Baseline and monthly evaluations over 12 months post-implantation
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: University of São Paulo General Hospital
state: SP
Study officials:
affiliation: University of Sao Paulo
name: Guilherme Alves Lepski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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