Supraspinal Control of Lower Urinary Tract Function in Healthy Controls and Patients With Bladder Dysfunction
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01768910 |
|
Recruitment Status :
Completed
First Posted : January 16, 2013
Last Update Posted : March 18, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neurogenic Lower Urinary Tract Dysfunction Multiple Sclerosis Overactive Bladder Spinal Cord Injury | Other: fMRI Other: bladder filling Other: bladder cooling Other: additional post-treatment fMRI scan | Not Applicable |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 91 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | December 2011 |
| Actual Primary Completion Date : | July 17, 2015 |
| Actual Study Completion Date : | December 2018 |
| 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.
|
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
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.
|
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
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.
|
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
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)
|
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 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
|
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 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. |
- 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.
- 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.
- Side effects [ Time Frame: 3 years ]Pain, Lower urinary tract infection
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01768910
| Switzerland | |
| Neuro-Urology, Spinal Cord Injury Center & Research, University of Zürich, Balgrist University Hospital | |
| Zürich, Switzerland, 8008 | |
| University Hospital Zürich | |
| Zürich, Switzerland, 8008 | |
| 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 |
| Responsible Party: | University of Zurich |
| ClinicalTrials.gov Identifier: | NCT01768910 |
| Other Study ID Numbers: |
KEK-ZH-2011-0346/PB_2016-00872 |
| First Posted: | January 16, 2013 Key Record Dates |
| Last Update Posted: | March 18, 2019 |
| Last Verified: | March 2019 |
|
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 |
|
Multiple Sclerosis Spinal Cord Injuries Urinary Bladder, Overactive Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases |
Immune System Diseases Spinal Cord Diseases Central Nervous System Diseases Trauma, Nervous System Wounds and Injuries Urinary Bladder Diseases Urologic Diseases Lower Urinary Tract Symptoms Urological Manifestations |