Treatment of Neurogenic Detrusor Overactivity: Early Versus Late Pudendal Nerve Stimulation in Spinal Cord Injury (SCI) Patients

Study Overview
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Brief Summary
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Background: Although a small group, special attention has to be given to lower urinary tract (LUT) dysfunctions in spinal cord injury (SCI) patients, as they also suffer under a loss of motor-sensory function and autonomic regulation next to the severe deficiencies in bladder and bowel control. Autonomic dysregulation linked with LUT dysfunction can cause autonomic dysreflexia with life threatening increases in blood pressure and there is still no concept for an early rehabilitation of bladder function after SCI. Hypothesis: We assume that inadequate reorganization of nerve fibres in SCI is a reason for spastic bladder dysfunction and vegetative dysregulation and that this can be positively influenced by early neuromodulation. We hypothesized that bladder dysfunction as well as autonomic dysreflexia will be positively affected. Specific aims: Evaluation, if external pudendal nerve stimulation (EPS) can positively influence LUT rehabilitation in SCI patients and if early initiation of stimulation is more effective compared to late initiation (after spinal shock). Experimental design: Prospective multicentre study in 36 SCI patients (24 treatment subjects, 12 control subjects). EPS will be started either within 10 days after SCI (early stim group) or after cessation of spinal shock (late stim group). Effects on spastic bladder function and autonomic disinhibition will be assessed by urodynamics, vegetative tests, and by electrophysiological techniques. Expected value: If early EPS is effective and complete SCI patients benefit from this intervention; and if early onset of EPS has better and longer lasting effects than late onset stimulation, the findings will be of utmost relevance not only for bladder function but also to alleviate adverse phenomena such as autonomic dysreflexia. Neurostimulation may bear the opportunity to early reshape maladaptive neuroplasticity. This would be proof of an effective modulation and promotion of neuroplasticity, thus opening up new treatment options in the field of paraplegiology.

Official Title
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Therapeutic Effects of Early and Late Onset Peripheral Pudendal Neurostimulation on Bladder Function and Autonomic Neuroplasticity in SCI - a Controlled European Multicenter Study

Conditions
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Neurogenic Detrusor Overactivity, Spinal Cord Injury

Intervention / Treatment
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* Procedure: external electric pudendal nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single event traumatic or ischemic Para- or Tetraplegia Complete SCI (ASIA A) Lesion level between C4 and Th10 Performance of study treatment and assessments possible according to the study time schedule Patient capable and willing of giving written informed consent Exclusion Criteria: Nontraumatic Para- or Tetraplegia (i.e. disc herniation, tumor, AV- Malformation, myelitis) exkl. single event ischemic incidences Pre- known dementia or severe reduction of intelligence, leading to reduced capabilities of cooperation or giving consent Peripheral Nerve lesions below the level of lesion (i.e. pudendal nerve impairment, cauda equina syndrome, pre- known Polyneuropathy) Severe craniocerebral injury Previous or planned intradetrusor injections of botulinum toxin Previous or planned surgical therapy for neurogenic detrusor overactivity (e.g. bladder augmentation, Mitrofanoff, sphincter prothesis, sacral neuromodulation, deafferentation, sphincterotomy)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early pudendal stimulation<br>Subjects in this arm will start with the intervention within 2 weeks after SCI | Procedure: external electric pudendal nerve stimulation<br>* intervention timing: twice daily for 20 minutes during 3 consecutive months. intervention procedure: electrodes will be placed around the penile shaft (in males) or clips will be directly placed on the clitoris (in females). intervention device: contic+ stimulation parameters: 10 Hz, 200μs pulse width, 10mA (or less, if too uncomfortable).<br>* Other names: contic+, tic Medizintechnik GmbH, 46286 Dorsten, Germany;|
| Experimental: Late pudendal stimulation<br>Subjects in this arm will start with the intervention 12 weeks after SCI | Procedure: external electric pudendal nerve stimulation<br>* intervention timing: twice daily for 20 minutes during 3 consecutive months. intervention procedure: electrodes will be placed around the penile shaft (in males) or clips will be directly placed on the clitoris (in females). intervention device: contic+ stimulation parameters: 10 Hz, 200μs pulse width, 10mA (or less, if too uncomfortable).<br>* Other names: contic+, tic Medizintechnik GmbH, 46286 Dorsten, Germany;|
| No Intervention: Control<br>Subjects in this arm will be treated according to standard therapy but will receive no pudendal stimulation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Videocystometry |  | week 4, 12, 26, 38, 52 after SCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurophysiological measurements (NCV, BCR, SSR) |  | week 2, 4, 12, 26, 38, 52 after SCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuromodulation, neurogenic detrusor overactivity, spinal cord injury, pudendal nerve stimulation, videocystometry, neurophysiology, neuroplasticity