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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Spinal Cord Injury; Neurogenic Detrusor Overactivity
• Intervention / Treatment: Procedure: external electric pudendal nerve stimulation

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Guttmann Institute
• Switzerland
  • Zurich, Switzerland, 8008
    • Balgrist University Hospital
  • Luzern
    • Nottwil, Luzern, Switzerland, 6207
      • Schweizerisches Paraplegikerzentrum Nottwil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early pudendal stimulation; Subjects in this arm will start with the intervention within 2 weeks after SCI	Procedure: external electric pudendal nerve stimulation; 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).; Other Names: contic+, tic Medizintechnik GmbH, 46286 Dorsten, Germany
Experimental: Late pudendal stimulation; Subjects in this arm will start with the intervention 12 weeks after SCI	Procedure: external electric pudendal nerve stimulation; 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).; Other Names: contic+, tic Medizintechnik GmbH, 46286 Dorsten, Germany
No Intervention: Control; Subjects in this arm will be treated according to standard therapy but will receive no pudendal stimulation

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ulrich Mehnert
• Collaborators: Institut Guttmann; Schweizerisches Paraplegikerzentrum Nottwil; BG Unfallklinik Murnau; Klinik für Paraplegiologie, Universitätsklinikum Heidelberg
• Investigators: Principal Investigator: Ulrich Mehnert, MD, University of Zurich; Principal Investigator: Martin Schubert, MD, Balgrist University Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: January 6, 2010
• First Submitted That Met QC Criteria: January 6, 2010
• First Posted (Estimate): January 7, 2010

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: neuroplasticity; neuromodulation; spinal cord injury; neurogenic detrusor overactivity; neurophysiology; pudendal nerve stimulation; videocystometry
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Urinary Bladder, Overactive; Spinal Cord Injuries
• Other Study ID Numbers: EMSCI-NU-2/09