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Supraspinal Control of Lower Urinary Tract Function in Healthy Controls & Patients With Bladder Dysfunction (2011-0346)

This study is currently recruiting participants.
Verified January 2013 by University of Zurich
Sponsor:
Collaborators:
Balgrist University Hospital
Swiss National Science Foundation
Information provided by (Responsible Party):
University of Zurich
ClinicalTrials.gov Identifier:
NCT01768910
First received: January 8, 2013
Last updated: January 28, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention
Neurogenic Lower Urinary Tract Dysfunction
Multiple Sclerosis
Overactive Bladder
 Other: fMRI
Other: bladder filling
Other: bladder cooling
Other: additional post-treatment fMRI scan

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Bladder and the Brain - Investigation of the Supraspinal Neural Control of Lower Urinary Tract Function in Healthy Subjects and Patients With Neurogenic and Non-neurogenic Bladder Dysfunction Using Advanced Neuroimaging Techniques

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Bold signal [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]

    During two fMRI measurements the changes of BOLD signal intensity in certain supraspinal areas (e.g. pons, insula, anterior cingulate cortex, thalamus, supplementary motor area, prefrontal cortex) in response to different bladder filling tasks will be evaluated.

    A third fMRI measurement might be applicable in NNOAB patients who received a study independent OAB treatment.

    Variables are age, bladder volume, urgency and attention.


  • Structural and functional connectivity [ Time Frame: baseline and after potential OAB treatment ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Side effects [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Pain, Lower urinary tract infection


Estimated Enrollment: 77
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy controls
fMRI, bladder filling, bladder cooling
 Other: fMRI
2 measurements using functional magnetic resonance imaging in a 3T scanner
Other: bladder filling
Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.
Other: bladder cooling
Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.
Experimental: MS without OAB
fMRI, bladder filling, bladder cooling
 Other: fMRI
2 measurements using functional magnetic resonance imaging in a 3T scanner
Other: bladder filling
Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.
Other: bladder cooling
Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.
Experimental: MS with OAB
fMRI, bladder filling, bladder cooling
 Other: fMRI
2 measurements using functional magnetic resonance imaging in a 3T scanner
Other: bladder filling
Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.
Other: bladder cooling
Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.
Experimental: NNOAB
fMRI, bladder filling, bladder cooling
 Other: fMRI
2 measurements using functional magnetic resonance imaging in a 3T scanner
Other: bladder filling
Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.
Other: bladder cooling
Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.
Other: additional post-treatment fMRI scan
Should NNOAB 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.

Detailed Description:

The subject recruitment will be performed within the Neuro-Urology outpatient clinic at the Balgrist University Hospital and in collaboration with the Departments of Neurology, Urology and Gynecology at the University Hospital Zürich.

After inclusion, all subjects and patients will undergo two functional magnetic resonance imaging (fMRI) sessions. Non-neurogenic overactive bladder (NNOAB) patients might undergo an additional fMRI session after receiving potential study independent overactive bladder (OAB) treatment.

High-resolution anatomical images and functional blood-oxygen-level-dependent (BOLD)-signal sensitive images will be acquired. In addition to the fMRI, diffusion tensor imaging (DTI) sequences will be recorded after the anatomical scans to provide information about the structural supraspinal connectivity.

Study endpoints are changes of the BOLD signal in regard to location and intensity, structural and functional connectivity (FC) between previously described supraspinal centers involved in LUT control, and statistical differences of changes in BOLD signals, structural and functional connectivity between patients and healthy controls.

All acquired fMRI data will be transferred to an off-line workstation running BrainVoyager QX or Statistical Parametric Mapping (SPM) Version 8. The functional data will be pre-processed for motion correction, spatial smoothing, linear trend removal, and temporal high-pass filtering. With both programs statistical analysis and graphical presentation of the results can be performed.

The DTI records will be evaluated with SPM8, BrainVoyager QX or other programs like Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) and DTI-Studio. To estimate FC we will use SPM8 or the brain connectivity toolbox. Both softwares allow the estimation of rest- and task-related connectivity on single subject and group level with corrected statistical threshold.

Overall, 70 subjects [20 healthy, 20 NNOAB patients and 30 neurogenic bladder dysfunction, i.e. multiple sclerosis (MS) patients] for the main study are estimated to be sufficient to demonstrate significant differences between groups.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy controls

  • Right handed
  • functional magnetic resonance (MR) suitability
  • Written informed consent
  • unimpaired LUT function

  • no LUT symptoms

    • ≤ 3 episodes of urinary urgency
    • frequency < 8/24h
  • no detrusor overactivity

MS patients with OAB

  • Right handed
  • functional 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

MS patients without OAB

  • Right handed
  • functional MR suitability
  • Written informed consent
  • diagnosis of MS according to the McDonald criteria
  • Expanded Disability Status Scale (EDSS) ≤ 6

  • no LUT symptoms

    • ≤ 3 episodes of urinary urgency
    • frequency ≤ 8/24h
  • no detrusor overactivity

Patients with NNOAB

  • Right handed
  • functional MR suitability
  • Written informed consent

  • idiopathic OAB symptoms since > 6 months

    • ≥ 3 episodes of urinary urgency
    • frequency > 8/24h
  • refractory to antimuscarinic treatment for ≥ 1 month
  • indication for intradetrusor injections of Botulinumtoxin Type A
  • willingness and ability to perform self-catheterization

Exclusion Criteria:

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
  • detrusor overactivity

MS patients with OAB

  • pregnancy or breast feeding
  • any permanent ferromagnetic implant
  • any neurological or psychological disease despite MS
  • any craniocerebral injury or surgery
  • any previous surgery of the LUT or genitalia
  • any anatomical anomaly or malignancy of the LUT or genitalia
  • any metabolic disease
  • PVR > 150ml
  • any concomitant treatment for the LUT (e.g. neuromodulation)
  • Stress urinary incontinence
  • any condition other than MS that might explain OAB symptoms
  • current urinary tract infection
  • indwelling catheters or the necessity to perform self-catheterization

MS patients without OAB

  • pregnancy or breast feeding
  • any permanent ferromagnetic implant
  • any neurological or psychological disease despite MS
  • any craniocerebral injury or surgery
  • any previous surgery of the LUT or genitalia
  • any anatomical anomaly or malignancy of the LUT or genitalia
  • any metabolic disease
  • PVR > 150ml
  • any concomitant treatment for the LUT (e.g. neuromodulation)
  • Stress urinary incontinence

  • any LUT symptoms

    • ≥ 3 episodes of urinary urgency
    • frequency > 8/24h
  • indwelling catheters or the necessity to perform self-catheterization
  • detrusor overactivity
  • current urinary tract infection

Patients with NNOAB

  • pregnancy or planned within next 8 months, breast feeding
  • any permanent ferromagnetic implant
  • any neurological, psychological, metabolic or cardiovascular disease
  • any craniocerebral injury or surgery
  • any previous surgery of the LUT or genitalia within the last year or that is related to the OAB symptoms
  • any anatomical anomaly or malignancy of the LUT or genitalia
  • PVR > 150ml
  • Stress urinary incontinence
  • indwelling catheters or the necessity to perform self-catheterization
  • any concomitant treatment for the LUT (e.g. neuromodulation)
  • current urinary tract infection
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01768910

Contacts
Contact: Matthias Walter +41 44 386 3721 mwalter@paralab.balgrist.ch
Contact: Thomas M Kessler, MD +41 44 386 3845 thomas.kessler@balgrist.ch

Locations
Switzerland
Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital Recruiting
Zürich, Switzerland, 8008
Contact: Matthias Walter     +41 44 386 3721     mwalter@paralab.balgrist.ch    
Contact: Thomas M Kessler, MD     + 44 386 3845     thomas.kessler@balgrist.ch    
Principal Investigator: Ulrich Mehnert, MD            
Principal Investigator: Thomas M Kessler, MD            
Principal Investigator: Spyros Kollias, MD            
University Hospital Zürich Recruiting
Zürich, Switzerland, 8091
Contact: Walter Matthias     +41 44 386 3721     mwalter@paralab.balgrist.ch    
Principal Investigator: Thomas M Kessler, MD            
Principal Investigator: Ulrich Mehnert, MD            
Principal Investigator: Spyros Kollias, MD            
Sponsors and Collaborators
University of Zurich
Balgrist University Hospital
Swiss National Science Foundation
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01768910     History of Changes
Other Study ID Numbers: 2011-0346
Study First Received: January 8, 2013
Last Updated: January 28, 2013
Health Authority: Switzerland: Ethikkommission

Keywords provided by University of Zurich:
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

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Urinary Bladder, Overactive
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
 Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on May 16, 2013