Supraspinal Control of Lower Urinary Tract Function in Healthy Controls and Patients With Bladder Dysfunction

NCT01768910 | Completed

• 1 other identifier: KEK-ZH-2011-0346/PB_2016-00872
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to provide profound insight into the supraspinal neuronal mechanisms and networks responsible for lower urinary tract (LUT) control and to verify, amend or adjust neuronal circuitry models established from findings in healthy subjects in the context of neurogenic and non-neurogenic LUT dysfunction.

Conditions

Neurogenic Lower Urinary Tract Dysfunction; Multiple Sclerosis; Overactive Bladder; Spinal Cord Injury

Keywords

lower urinary tract; bladder; supraspinal control; neuroimaging; functional magnetic resonance imaging; diffusion tensor imaging; functional connectivity; neurogenic lower urinary tract dysfunction; overactive bladder; multiple sclerosis; spinal cord injury

Outcome Measures

Primary Outcomes (2)

• Bold signal

  During fMRI measurements the changes of BOLD signal intensity in respect to certain supraspinal areas (e.g. pons, insula, anterior cingulate cortex, thalamus, supplementary motor area, prefrontal cortex) will be evaluated. Variables are age, bladder volume, urgency and attention.

  baseline and 4 weeks

• Structural and functional connectivity

  Acquired data from the above mentioned measurements will be used to analyze structural and functional connectivity between supraspinal areas involved in the LUT control, especially between prefrontal, thalamus, insula, and anterior cingulate cortex. Variables are age, bladder volume, urgency and attention. Correlations of neuronal activity from the fMRI-data will be estimated using SPM8, brain connectivity tool box.

  baseline and after potential OAB treatment

Secondary Outcomes (1)

• Side effects

  3 years

Study Arms (5)

Healthy controls

EXPERIMENTAL

Procedure: 1-2 fMRI measurements within 4 weeks from first exam. Measurements include repetitive retrograde bladder filling via transurethral catheter at different bladder volumes and temperatures (e.g. bladder cooling, body warm or room temperature)of the filling liquid.

Other: fMRI; Other: bladder filling; Other: bladder cooling

MS with OAB

EXPERIMENTAL

Procedure: 1-2 fMRI measurements within 4 weeks from first exam. Measurements include repetitive retrograde bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid.

Other: fMRI; Other: bladder filling; Other: bladder cooling

MS without OAB

EXPERIMENTAL

Procedure: 1-2 measurements within 4 weeks from first exam. Measurements include repetitive bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid.

Other: fMRI; Other: bladder filling; Other: bladder cooling

NNOAB

EXPERIMENTAL

Procedure: 1-2 measurements within 4 weeks from first exam. Measurements include repetitive bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid plus additional post-treatment fMRI scan 5 to 7 weeks after OAB treatment (such as antimuscarinics, intradetrusor injections of botulinum toxin type A)

Other: fMRI; Other: bladder filling; Other: bladder cooling; Other: additional post-treatment fMRI scan

SCI with neurogenic detrusor overactivity

EXPERIMENTAL

Procedure: 1-2 measurements within 4 weeks from first exam. Measurements include repetitive bladder filling via transurethral catheter at different bladder volumes and temperatures of the filling liquid plus 1 additional post-treatment fMRI scan 5 to 7 weeks after intradetrusor injections of botulinum toxin type A

Other: fMRI; Other: bladder filling; Other: bladder cooling; Other: additional post-treatment fMRI scan

Interventions

fMRI OTHER

2 measurements using functional magnetic resonance imaging in a 3T scanner

Healthy controls; MS with OAB; MS without OAB; NNOAB; SCI with neurogenic detrusor overactivity

bladder filling OTHER

Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.

Healthy controls; MS with OAB; MS without OAB; NNOAB; SCI with neurogenic detrusor overactivity

bladder cooling OTHER

Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.

Healthy controls; MS with OAB; MS without OAB; NNOAB; SCI with neurogenic detrusor overactivity

additional post-treatment fMRI scan OTHER

Should NNOAB or SCI patients receive a study independent OAB therapy by their treating physician after the 2nd fMRI scan, they will be invited for an additional third fMRI scan.

NNOAB; SCI with neurogenic detrusor overactivity

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy controls
• Right handed
• MR suitability
• Written informed consent
• unimpaired LUT function
• MS patients with OAB
• Right handed
• MR suitability
• Written informed consent
• diagnosis of MS according to the McDonald criteria
• Expanded Disability Status Scale (EDSS) ≤ 6
• OAB symptoms since \> 6 months
• ≥ 3 episodes of urinary urgency
• frequency \> 8/24h
• with or without detrusor overactivity

You may not qualify if:

• Healthy controls
• impaired LUT function
• pregnancy or breast feeding
• no informed consent
• any craniocerebral injury or surgery
• any permanent ferromagnetic implant
• any previous surgery of the LUT or genitalia
• any anatomical anomaly of the LUT or genitalia
• any LUT malignancy
• postvoid residual urine volume (PVR) \> 150ml
• current urinary tract infection
• any LUT symptoms
• ≥ 3 episodes of urinary urgency
• frequency \> 8/24h
• MS patients with OAB

Sponsors & Collaborators

• University of Zurich: lead
• Swiss National Science Foundation: collaborator
• Balgrist University Hospital: collaborator

Study Sites (2)

Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital

Zurich, 8008, Switzerland

Location

University Hospital Zürich

Zurich, 8008, Switzerland

Location

Related Publications (4)

• Walter M, Michels L, Kollias S, van Kerrebroeck PE, Kessler TM, Mehnert U. Protocol for a prospective neuroimaging study investigating the supraspinal control of lower urinary tract function in healthy controls and patients with non-neurogenic lower urinary tract symptoms. BMJ Open. 2014 May 21;4(5):e004357. doi: 10.1136/bmjopen-2013-004357.

  PMID: 24848086 RESULT

• Leitner L, Walter M, Freund P, Mehnert U, Michels L, Kollias S, Kessler TM. Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity. BMC Urol. 2014 Aug 18;14:68. doi: 10.1186/1471-2490-14-68.

  PMID: 25132340 RESULT

• Leitner L, Walter M, Jarrahi B, Wanek J, Diefenbacher J, Michels L, Liechti MD, Kollias SS, Kessler TM, Mehnert U. A novel infusion-drainage device to assess lower urinary tract function in neuro-imaging. BJU Int. 2017 Feb;119(2):305-316. doi: 10.1111/bju.13655. Epub 2016 Oct 20.

  PMID: 27617867 RESULT

• Walter M, Leitner L, Michels L, Liechti MD, Freund P, Kessler TM, Kollias S, Mehnert U. Reliability of supraspinal correlates to lower urinary tract stimulation in healthy participants - A fMRI study. Neuroimage. 2019 May 1;191:481-492. doi: 10.1016/j.neuroimage.2019.02.031. Epub 2019 Feb 15.

  PMID: 30776530 RESULT

MeSH Terms

Conditions

Multiple Sclerosis; Urinary Bladder, Overactive; Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Spinal Cord Diseases; Central Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Ulrich Mehnert, MD

  Neuro-Urology, Spinal Cord Injury Center & Research, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland

  PRINCIPAL INVESTIGATOR

• Thomas M Kessler, MD

  Neuro-Urology, Spinal Cord Injury Center & Research, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland

  PRINCIPAL INVESTIGATOR

• Spyros Kollias, MD

  Institute of Neuroradiology, University Hospital Zurich, Sternwartstrasse 6, 8091 Zurich, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 16, 2013
• Study Start: December 1, 2011
• Primary Completion: July 17, 2015
• Study Completion: December 1, 2018
• Last Updated: March 18, 2019

Record last verified: 2019-03

Locations

CH (2)