Supraspinal Control of Lower Urinary Tract Function in Healthy Controls and Patients With Bladder Dysfunction
Condition: Neurogenic Lower Urinary Tract Dysfunction; Multiple Sclerosis; Overactive Bladder; Spinal Cord Injury
MeSH terms: Multiple Sclerosis; Spinal Cord Injuries; Urinary Bladder, Overactive; Sclerosis
Study type: Interventional

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.
    

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.

      The following subject groups will be recruited: 1) healthy controls (n=22), Non-neurogenic
      overactive bladder (NNOAB) patients (n=20), multiple sclerosis (MS) patients with OAB (n=15),
      MS patients without OAB (n=15), spinal cord injury (SCI) patients with neurogenic detrusor
      overactivity (n=24).

      After inclusion, all subjects and patients will undergo one to two functional magnetic
      resonance imaging (fMRI) sessions. NNOAB patients might undergo an additional fMRI session
      after receiving overactive bladder (OAB) treatment (such as antimuscarinics, intradetrusor
      injections of botulinum toxin type A). Spinal cord injury (SCI) patients with neurogenic
      detrusor overactivity will undergo an additional fMRI session 5-7 weeks after intradetrusor
      injections of botulinum toxin type A.

      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, 96 subjects for the main study are estimated to be sufficient to demonstrate
      significant differences between groups.
    

Intervention name(s): fMRI; bladder filling; bladder cooling; additional post-treatment fMRI scan
Intervention type(s): Other; Other; Other; Other
Intervention description(s): 2 measurements using functional magnetic resonance imaging in a 3T scanner; Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.; Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.; 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.
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
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