Clinical trial NCT02978638: Electrical Stimulation for Continence After Spinal Cord Injury
Official title: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injury
Neurogenic Bladder
Incontinence
Keywords: Spinal cord injury
Bladder capacity
Electrical stimulation
Continence
Urodynamics
Lead sponsor: Palo Alto Veterans Institute for Research
Sponsor class: OTHER
Collaborators: name: VA Palo Alto Health Care System
name: Stanford University
name: Case Western Reserve University
name: Santa Clara Valley Medical Center
name: University of New Mexico
First posted: 2016-12-01
Enrollment: 10
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to improve continence and voiding of patients with spinal cord injury using electrical stimulation.

The Finetech Vocare Bladder System is an implantable sacral nerve stimulator for improving bladder and bowel function in patients with spinal cord injury (SCI). It has been commercially available in Britain and other countries since 1982, and has been used in thousands of patients with SCI to improve bladder, bowel and sexual function. It received FDA approval in 1998 under Humanitarian Device Exemption H980005 and H980008 for providing urination on demand and to aid in bowel evacuation.

Electrical stimulation to produce bladder contraction and improve bladder voiding after spinal cord injury has usually been combined with cutting of sensory nerves to reduce reflex contraction of the bladder, which improves continence. However, cutting these nerves has undesirable side effects. This study will not cut any sensory nerve. This study is testing the use of the stimulator for inhibiting bladder contraction by stimulating sensory nerves to improve continence after spinal cord injury, and for blocking sphincter contraction to improve voiding.

Detailed description: Human subjects will be recruited from people with clinically complete spinal cord injury.

Subjects who meet the selection criteria described below will be screened to identify those whose reflex bladder contractions are inhibited by neuromodulation using low levels of electrical stimulation via electrodes on the skin over the dorsal genital nerve. Serial filling cystometries will be performed in the clinical urodynamic laboratories at the study sites. Bladder capacity and compliance will be recorded for each cytometrogram. Subjects whose reflex bladder contractions are significantly inhibited by this neuromodulation will be offered enrollment in the trial. Subjects whose reflex bladder contractions are not significantly inhibited by this neuromodulation, or who do not wish to participate in the study, will be able to continue with their usual form of bladder management.

After screening, selected subjects will be offered surgical implantation of a Vocare Bladder System in the FDA-approved manner, but without posterior rhizotomy. Because posterior rhizotomy is not performed, the afferent axons in the sacral nerves are intact and can be stimulated after surgery via the electrodes connected to the implanted stimulator.

The Vocare Bladder System will be implanted in the FDA-approved manner but without posterior rhizotomy.

After implantation, subjects will be evaluated in the urodynamic laboratory. Stimulation will applied to S34 sacral nerves bilaterally, and the effects on bladder capacity and continence and voiding will be measured.

Continence of urine will be documented by bladder diaries. These diaries will be completed initially as an inpatient in the SCI Service and then at home while applying neuromodulation via the implant.

It is expected that sacral neuromodulation by this method will be associated with a significant increase in bladder capacity and continence.

It is possible that this neuromodulation will not be associated with an increase in bladder capacity or continence. If so, subjects will still be able to use conventional methods of managing continence and should have no loss of function.

Participants whose bladder capacity and continence are improved by neuromodulation using the implanted stimulator will be offered the opportunity to continue to use the stimulator for the duration of the study and will be reviewed at three-month intervals. At the end of the study they will be reviewed again with their usual clinician and if there are no contra-indications to continued use of the stimulator will be offered the opportunity to continue its use under continued clinical follow-up from their usual clinician.

Participants whose bladder capacity and continence are not improved by neuromodulation using the implanted stimulator, or who do not wish to continue using the implanted stimulator, will be reviewed with their usual clinician and offered the bladder management they were using prior to the study. The implanted stimulator will be switched off, but will not be removed unless the participant wishes it to be removed or the investigators or the participant's usual clinician consider it in the participant's interest to be removed. It is usually simpler and safer for the participant to leave the stimulator implanted but inactive.

All participants will be provided with appropriate documentation regarding safety and electromagnetic compatibility of the device.

The investigation is justified because the potential benefits are greater than the potential risks, as follows:

The potential benefit of the research to the subjects are:

1. Improved bladder capacity
2. Improved continence

The potential benefits of the research to others are:

Evidence that bladder capacity and continence after spinal cord injury can be improved by electrical stimulation without cutting nerves.

The risks to subjects are reasonable in relation to the anticipated benefits to subjects and others because of

1. The high prevalence and severity of clinical complications caused by bladder complications after spinal cord injury
2. The paucity of methods of restoring continence after spinal cord injury that are safe, effective and without undesirable side effects

This study is primarily aimed at demonstrating safety, feasibility and proof of concept. It may also produce statistically and clinically significant evidence of efficacy that can be used to plan future clinical trials.

Significance:

If the technique of reducing reflex bladder contraction by implanted stimulation of the S34 nerve bilaterally is successful, it will open the door to more effective use of neuromodulation for continence after spinal cord injury.

Eligibility criteria: Inclusion Criteria:

Subjects will be included if they meet all of the following criteria:

* Complete spinal cord injury (AIS grade A) of at least 2 years duration with neurological level (ISNCSCI level) below C4
* Impaired bladder emptying due to Detrusor External Sphincter Dyssynergia-DESD (unco-ordinated contraction of bladder and external urethral sphincter) as shown on video-urodynamic testing.
* Impaired continence due to detrusor hyper-reflexia

Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:

* Absence of reflex contractions of the bladder as shown on urodynamic testing
* Absence of reflex contractions of the external urethral sphincter as shown on urodynamic testing with EMG
* External sphincterotomy, urethral stricture or previous urethral or sphincter or bladder or prostate surgery
* History of pelvic fracture
* Subjects on anticoagulants or with coagulation disorders
* Immunosuppressed subjects
* Active or recurrent pressure ulcers, particularly in sacral, ischial or trochanteric areas
* Active untreated infection
* Active implanted medical device such as cardiac pacemaker or defibrillator
* Progressive spinal cord injury
* Pregnancy
* Mechanical ventilator dependency
* Any other significant co-morbidity or illness that would preclude their participation or increase the risk to them of participating in the study
* Inability or unwillingness to follow study protocol or give informed consent

Primary outcomes:
measure: Bladder capacity
timeFrame: Change from baseline bladder capacity at 12-month follow-up visit
Secondary outcomes:
measure: Frequency of incontinence of urine
timeFrame: Change from baseline frequency of incontinence of urine at 12-month follow-up visit
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Palo Alto Veterans Institute for Research
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Medical Center
state: California
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
Study officials:
affiliation: Palo Alto Veterans Institute for Research
name: Graham H. Creasey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Reza Ehsanian, MD PhD
role: STUDY_DIRECTOR
References:
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citation: Ehsanian R, Creasey G, Elliott CS, Abu-Eid CA, Ali A, Prutton M, Singh H. Implantation of Sacral Nerve Stimulator Without Rhizotomy for Neurogenic Bladder in Patient With Spinal Cord Injury: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2020 Sep 1;19(3):E299. doi: 10.1093/ons/opz429.