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

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01768910
• Other study ID #: KEK-ZH-2011-0346/PB_2016-00872
• Status: Completed
• Phase: N/A
• Start date: December 2011
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: December 2018
• Est. primary completion date: July 17, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

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

MS patients without OAB

• Right handed

• MR suitability

• Written informed consent

• diagnosis of MS according to the McDonald criteria

• Expanded Disability Status Scale (EDSS) = 6

Patients with NNOAB

• Right handed

• 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

SCI patients with neurogenic detrusor overactivity

• Right handed

• MR suitability

• Written informed consent

• neurogenic detrusor overactivity due to SCI

• indication for intradetrusor injections of botulinum toxin type A

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

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

SCI patients with neurogenic detrusor overactivity

• pregnancy or breast feeding

• any permanent ferromagnetic implant

• any neurological or psychological disease despite SCI

• any craniocerebral injury or surgery

• any previous surgery of LUT of genitalia

• any anatomical anomaly or malignancy of the LUT or genitalia

• any metabolic disease

• any concomitant treatment for the LUT (e.g. neuromodulation)

• current urinary tract infection

Related Conditions & MeSH terms

• Multiple Sclerosis
• Neurogenic Lower Urinary Tract Dysfunction
• Overactive Bladder
• Sclerosis
• Spinal Cord Injuries
• Spinal Cord Injury
• Urinary Bladder, Overactive

Intervention

Other:
• fMRI
2 measurements using functional magnetic resonance imaging in a 3T scanner
• bladder filling
Repetitive retrograde bladder filling via transurethral catheter with different filling volumes using body warm saline during each of the fMRI measurements.
• bladder cooling
Retrograde bladder filling via transurethral catheter with 4-8°C saline during each of the fMRI measurements.
• additional post-treatment fMRI scan
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.

Locations

Country	Name	City	State
Switzerland	Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital	Zürich
Switzerland	University Hospital Zürich	Zürich

Sponsors (3)

Lead Sponsor	Collaborator
University of Zurich	Balgrist University Hospital, Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

References & Publications (4)

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 — View Citation

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 — View Citation

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 Feb 15;191:481-492. doi: 10.1016/j.ne — View Citation

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 urina — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Side effects	Pain, Lower urinary tract infection	3 years