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

Primary Purpose

Neurogenic Lower Urinary Tract Dysfunction, Multiple Sclerosis, Overactive Bladder

Status

Completed

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

fMRI

bladder filling

bladder cooling

additional post-treatment fMRI scan

About this trial

This is an interventional basic science trial for Neurogenic Lower Urinary Tract Dysfunction focused on measuring 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

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Healthy controls

MS with OAB

MS without OAB

NNOAB

SCI with neurogenic detrusor overactivity

Arm Description

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.

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)

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Side effects

Pain, Lower urinary tract infection

Full Information

NCT ID

NCT01768910

First Posted

January 8, 2013

Last Updated

March 14, 2019

Sponsor

University of Zurich

Collaborators

Swiss National Science Foundation, Balgrist University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01768910

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

December 2011 (Actual)

Primary Completion Date

July 17, 2015 (Actual)

Study Completion Date

December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Zurich

Collaborators

Swiss National Science Foundation, Balgrist University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

91 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy controls

Arm Type

Experimental

Arm Description

Arm Title

MS with OAB

Arm Type

Experimental

Arm Description

Arm Title

MS without OAB

Arm Type

Experimental

Arm Description

Arm Title

NNOAB

Arm Type

Experimental

Arm Description

Arm Title

SCI with neurogenic detrusor overactivity

Arm Type

Experimental

Arm Description

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

Intervention Type

Other

Intervention Name(s)

fMRI

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

bladder filling

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

bladder cooling

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

additional post-treatment fMRI scan

Intervention Description

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.

Primary Outcome Measure Information:

Title

Bold signal

Description

Time Frame

baseline and 4 weeks

Title

Structural and functional connectivity

Description

Time Frame

baseline and after potential OAB treatment

Secondary Outcome Measure Information:

Title

Side effects

Description

Pain, Lower urinary tract infection

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ulrich Mehnert, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Thomas M Kessler, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Spyros Kollias, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Zürich

ZIP/Postal Code

8008

Country

Switzerland

Facility Name

University Hospital Zürich

City

Zürich

ZIP/Postal Code

8008

Country

Switzerland

12. IPD Sharing Statement

Citations:

PubMed Identifier

24848086

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 urinary tract symptoms. BMJ Open. 2014 May 21;4(5):e004357. doi: 10.1136/bmjopen-2013-004357. Erratum In: BMJ Open. 2014;4(6):e004357.

Results Reference

result

PubMed Identifier

25132340

Citation

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.

Results Reference

result

PubMed Identifier

27617867

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.13655. Epub 2016 Oct 20.

Results Reference

result

PubMed Identifier

30776530

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 May 1;191:481-492. doi: 10.1016/j.neuroimage.2019.02.031. Epub 2019 Feb 15.

Results Reference

result

Learn more about this trial

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

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