Study on Preliminary Safety and Efficacy of Epidural Electrical Stimulation to Manage Lower Urinary Tract Dysfunction After Spinal Cord Injury

Ecole Polytechnique Fédérale de Lausanne3 enrolled

Overview

This clinical trial aims to assess the preliminary safety and efficacy of Epidural Electrical Stimulation (EES) therapy in managing lower urinary tract dysfunction in individuals with sub-acute or chronic spinal cord injury (SCI). The study evaluates the therapy's potential to improve urinary function and prevent neurogenic detrusor overactivity, ultimately seeking to enhance quality of life for individuals with SCI.

The consequences of a Spinal Cord Injury (SCI) are dramatic. SCI leads to impairment of motor, sensory, and autonomic systems, dysregulating almost every bodily function below the level of injury. The majority of research on SCI focuses on the restoration of movement. However, the disruption of pathways controlling the bladder leads to less-appreciated symptoms that require life-long clinical management, are the one of the main cause of rehospitalization, and incurred the largest healthcare costs after SCI. Neurogenic bladder issues, such as neurogenic detrusor overactivity (NDO) leading to incontinence, detrusor-sphincter dyssynergia (DSD) and decreased bladder compliance, are currently treated with intermittent catheterization, anticholinergic medications, botulinum toxin injections directly into the detrusor and ultimately irreversible major surgical interventions. Despite improvement in bladder management provided by these clinical and interventional tools, people with SCI still experience recurrent urinary tract infections from repeated catheterization, incontinence events impacting their professional and intimate life, side-effects from anti-cholinergic medication. It therefore comes as no surprise that people with spinal cord injury prioritize the treatment of lower urinary tract dysfunction as one of their top health priorities. The investigators reasoned that the neuroprosthetic management of micturition and urinary continence may overcome many of the existing limitations of current clinical management strategies. To test this idea, the investigators have developed a neuroprosthetic system based on Epidural Electrical Stimulation (EES) of the spinal cord that restored micturition (EESVOIDING) and improve urinary continence by reducing detrusor overactivity (EESSTORAGE) in preclinical models of SCI. Development of this neuroprosthetic system combined with rigorous experiments led to the identification of the locations and parameters of EES that can activate the detrusor while relaxing the external urethral sphincter (EUS). The investigators also gathered preliminary evidence on the key features of this therapeutic strategy in one patient with low-thoracic motor-complete SCI (T10, AIS-B) who was implanted with a neuroprosthetic system on the lumbosacral spinal cord (covering T12 to S1) to restore walking (STIMO clinical Trial, NCT02936453). Stimulation of the sacral spinal cord of this participant resulted in controlled detrusor contraction leading to voiding. Consequently, the investigators hypothesize that EES has the potential to become the first-line treatment for bladder dysfunction in people with chronic or sub-acute SCI. However, its clinical deployment relies on selective stimulation paradigms and development of medical-grade implantable spinal-cord stimulation technologies that are optimized for bladder management. The ReeVoid clinical study will enroll 3 participants, who will be implanted with a system to apply EES to stimulate the spinal circuits involved in the control of the bladder. The aim of the study is to manage lower urinary tract functions with EES, including supporting voiding and preventing neurogenic detrusor overactivity incontinence (NDOI) in individuals with sub-acute or chronic spinal cord injury located above T11 and who suffer from lower urinary tract dysfunction. Two electrode paddle leads will be implanted. The first one will cover the dorsal root entry zone of the lumbosacral segments (L4-S5), while the second will aim to target the S1-S4 roots where they exit the spinal canal in the lower vertebras, and thus to maximise selective recruitment of the dorsal roots involved in the control of the detrusor and urethral sphincter muscles. Each paddle lead will be connected to a neurostimulator located subcutaneously in the region of the abdomen. This therapy aims also to have a positive impact on other neurological functions such as sexual function, bowel management and muscle tone normalization (reduced spasticity).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 or older; * Must provide and sign the Informed Consent Form prior to any study-related procedures; * Spinal cord injury lesion level above T11 (inclusive); * SCI graded as AIS- B, C or D; * SCI ≥ 6 months; * Confirmed lower urinary tract dysfunction during urodynamic assessment (NDO, DSD); * Intolerant, refractory or inefficient to conservative treatment options such as medications and behavioural management; * Using intermittent self-catheterization; * Stable medical, physical and psychological condition as considered by the investigators; * Able to understand and interact with the study team in French or English; * Agrees to comply in good faith with all conditions of the study and to attend all scheduled appointments; Exclusion Criteria: * Botulinum toxin vesical injections in the previous 6 months; * Presence of non-pharmacological treatments for lower urinary tract dysfunction (e.g. sacral nerve stimulation); * Does have or needs a suprapubic catheter or bladder indwelling catheter; * Presence of upper urinary tract dilatation or bladder or renal stones; * Presence of urethral stricture or significant benign prostate hyperplasia; * Presence of significant pressure ulcers; * Previous lower urinary tract surgery; * Presence of Autonomic Dysreflexia during urodynamic test; * Recurrent and symptomatic urinary tract infection (more than 3 per year); * Presence of intrathecal baclofen pump; * Diseases and conditions that would increase the morbidity and mortality of spinal surgery; * Other clinically significant concomitant disease states (e.g., syringomyelia, bladder cancer, renal failure, hepatic dysfunction, cardiovascular disease, etc.); * The inability to withhold antiplatelet/anticoagulation agents perioperatively; * Presence of pacemakers for cardiac conditions; * Other conditions that would make the subject unable to participate in testing in the judgement of the investigators; * Women who are pregnant (pregnancy test obligatory for woman of childbearing potential) or breast feeding; * Lack of acceptable or highly effective method of contraception for women of childbearing capacity; * Intention to become pregnant during the course of the study; * Inability to follow the procedures of the study, e.g. due to language problems, mental illness, psychological disorders, or dementia of the participant; * Participation in another study with investigational drug or device within the 30 days preceding and during the present study; * Have any indication that would require Magnetic Resonance Imaging (MRI) * Is the investigator himself, his/her family members, employees or other dependent persons.

Outcomes

Primary Outcomes

Occurrence of serious adverse events and adverse events.

Occurrence of serious adverse events and adverse events that are deemed related or possibly related to the use of the investigational.

Time frame: From enrolment through study completion, an average of 10 months.

Secondary Outcomes

ASIA impairment scale - International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)

Clinical examination used to assess the motor and sensory impairment and severity of a spinal cord injury.

Time frame: Pre-implantation (up to 3 weeks pre-implantation) and at the End of Study phase (lasting up to 1 week at 9 months)

Spasticity assessment (Modified Ashworth Scale - MAS)

Resistance of a muscle to a passive range of motion about a single joint, measured using the Modified Ashworth Scale (MAS), a 6-point scale with scores of 0, 1, 1+, 2, 3, and 4. A score of 0 indicates no increase in muscle tone, while a score of 4 indicates the affected part is rigid in flexion or extension. Higher scores indicate worse spasticity.

Time frame: Pre-implantation (up to 2 weeks pre-implantation) and at Follow-up phase and End of Study phase (at months 3, 6 and 9 post-implantation and lasting up to 1 week)

Daily Bladder related diary

Self-reported measures including urinary related events (voiding volume by catheterization and electrical stimulation, frequency, daytime and during night frequency, catheterization and volume of residual volume after stimulation, symptomatic urinary tract infection, use of stimulation) reported on a tracking app to quantify changes before and after implantation.

Time frame: Pre-implantation (up to 2 weeks pre-implantation), Mapping phase (1 week post-implantation and lasting up to 1 month), at Follow-up phase and End of Study phase (at months 3 and 6 post-implantation and lasting up to 1 week)

Renal ultrasound

Renal ultrasound is used to monitor the kidneys, ureters, and bladder, providing valuable information about kidney size, shape, and position.

Time frame: Pre-implantation (up to 3 weeks before implantation), Mapping phase (1 week post-implantation and lasting up to 1 month), Follow-up phase and End of Study phase (at months 3, 6 and 9 post-implantation and lasting up to 1 week)

Urine sampling

Urine sampling is taken to confirm the absence of any urinary tract.

Time frame: Pre-implantation (up to 3 weeks pre-implantation) and upon suspicion

24 hours urine collection

24 hours urine collection is taken to quantify the spot albumin and creatinine in the urine. These parameters are used to confirm the absence of any renal dysfunctions.

Time frame: Pre-implantation (up to 3 weeks pre-implantation) and at Follow-up phase and End of Study phase (at months 3, 6 and 9 post-implantation and lasting up to 1 week)

Blood samples

Blood sampling (max 20mL) is taken to quantify creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and cystatin C. These parameters are used to confirm the absence of any renal dysfunctions.

Time frame: Pre-implantation (up to 3 weeks pre-implantation) and at Follow-up phase and End of Study phase (at months 3, 6 and 9 post-implantation and lasting up to 1 week)

Cystometry

A catheter is inserted into the bladder to measure intravesical pressure while the bladder is filled with sterile fluid at a controlled rate. Simultaneously, abdominal pressure is monitored to assess detrusor pressure and bladder compliance. Cystometry helps identify neurogenic detrusor overactivity, bladder capacity, and compliance.

Time frame: Pre-implantation (up to 3 weeks and up to 2 weeks pre-implantation), Mapping phase (1 week post-implantation and lasting up to 1 month), at Follow-up phase and End of Study phase (at months 3, 6 and 9 post-implantation and lasting up to 1 week)

Imaging (with contrast agent)

X-Ray (or fluoroscopy) can be taken, with imaging contrast agents, to provide visualization of the urinary tract and/or catheter placements (optional).

Pressure-flow study

During voiding, simultaneous measurements of detrusor pressure and urinary flow rate are recorded. This aids in diagnosing detrusor-sphincter dyssynergia (DSD), evaluating voiding efficiency, and identifying obstructive patterns.

Electromyography (EMG)

Surface electrodes or specialized catheters are used to record electrical activity in the bladder and external urethral sphincter muscles. EMG helps detect detrusor-sphincter dyssynergia (DSD) by assessing the coordination between detrusor and sphincter activity during filling and voiding.

Flowmetry - Urethral pressure profile (UPP)

A catheter-mounted pressure sensor is withdrawn slowly from the bladder through the urethra, recording pressure changes along the urethral length. UPP assists in evaluating sphincter function and diagnosing urethral obstruction.

Study on Preliminary Safety and Efficacy of Epidural Electrical Stimulation to Manage Lower Urinary Tract Dysfunction After Spinal Cord Injury

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts