- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01768910
Supraspinal Control of Lower Urinary Tract Function in Healthy Controls and Patients With Bladder Dysfunction
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Zürich, Switzerland, 8008
- Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital
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Zürich, Switzerland, 8008
- University Hospital Zurich
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NON_RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Healthy controls
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.
|
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.
|
EXPERIMENTAL: MS with OAB
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.
|
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.
|
EXPERIMENTAL: MS without OAB
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.
|
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.
|
EXPERIMENTAL: NNOAB
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)
|
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.
|
EXPERIMENTAL: SCI with neurogenic detrusor overactivity
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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bold signal
Time Frame: baseline and 4 weeks
|
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
Time Frame: baseline and after potential OAB treatment
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Side effects
Time Frame: 3 years
|
Pain, Lower urinary tract infection
|
3 years
|
Collaborators and Investigators
Sponsor
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
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Central Nervous System Diseases
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Urologic Diseases
- Urinary Bladder Diseases
- Lower Urinary Tract Symptoms
- Urological Manifestations
- Wounds and Injuries
- Trauma, Nervous System
- Spinal Cord Diseases
- Multiple Sclerosis
- Sclerosis
- Urinary Bladder, Overactive
- Spinal Cord Injuries
Other Study ID Numbers
- KEK-ZH-2011-0346/PB_2016-00872
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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