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Central Nervous System Changes Following BotulinumtoxinA Injection in the Bladder

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ClinicalTrials.gov Identifier: NCT03033355
Recruitment Status : Recruiting
First Posted : January 26, 2017
Last Update Posted : April 9, 2018
Sponsor:
Collaborator:
The Methodist Hospital System
Information provided by (Responsible Party):
Rose Khavari, M.D., The Methodist Hospital System

Brief Summary:

The purpose of this prospective research study is to evaluate higher neural changes following intradetrusor injection of Botulinum toxin-A (BTX-A) in patients with Multiple Sclerosis (MS). Concurrent Urodynamic and Functional Magnetic Resonance (fMRI) data will be recorded pre- and post- intravesical injection of BTX-A in patients with Multiple Sclerosis (MS) and neurogenic detrusor activity (NDO).

Other objectives are to evaluate the role of urinary biomarkers such as brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF) associated with bladder overactivity and, to determine whether the common validated urgency questionnaires correlate with fMRI findings and urinary biomarker concentration pre- and post- BTX-A injection in patients with MS and NDO.


Condition or disease Intervention/treatment
Multiple Sclerosis Lower Urinary Tract Symptoms Neurogenic Bladder Detrusor, Overactive Urge Incontinence Drug: Intradetrusor injection of Botulinum Toxin-A

Detailed Description:

Multiple Sclerosis is a severe debilitating disease that affects patient's quality of life. Up to 90% of patients with MS will develop lower urinary tract dysfunction within the first 18 years of the disease. Lower urinary tract symptoms (LUTS) can range from urgency to urge urinary incontinence and/or hesitancy and incomplete bladder emptying. Urgency, frequency, and neurogenic detrusor overactivity (NDO) are the most common urologic findings (34-99%) during diagnostic evaluations of patients with MS. Even though anticholinergic or beta agonist drugs have limited effectiveness and adverse side effects, they are the first line pharmacotherapy for patients with NDO if behavioral modifications and pelvic floor physical therapy are unsuccessful. Botulinum toxin-A (BTX-A) intradetrusor injection is a highly effective treatment option for patients with NDO who are refractory to more conservative management. BTX-A blocks the release of acetylcholine at the neuromuscular junction and leads to a temporary chemodenervation of the bladder (paralysis of the muscle). Motor effects of BTX-A on the bladder have been extensively studied and widely reported in the literature, and the US Food and Drug Administration has approved BTX-A for the treatment of detrusor overactivity in neurogenic and non-neurogenic patients. However, the sensory effects of BTX-A injection correlating to central nervous system regional perception/localization of urgency, frequency, and urge incontinence in humans are not well known.

Over the past decades, functional MRI (fMRI) has been used to study the activation of supraspinal lower urinary tract control centers in healthy subjects during the storage and voiding phases. Given these facts, the investigators are interested in evaluating the role of intradetrusor injection of BTX-A in afferent response in patients with MS and NDO. High-resolution neuroimaging techniques will help investigators to further understand how MS affects the bladder-brain controls. This study will use fMRI and task-related blood oxygen level dependent (BOLD) signal to evaluate patients with MS and NDO prior to, and 6-10 weeks after intradetrusor injection of BTX-A with simultaneous urodynamic evaluation.

Clinical correlation between women with these chronic urologic problems and new discoveries at level of CNS activity will give a better understanding of this disorder, leading to the development of more effective diagnostic and treatment modalities.


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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Study of Higher Neural Control Changes Following Intradetrusor Injection of BotulinumtoxinA in Patients With Multiple Sclerosis and Lower Urinary Tract Symptoms.
Actual Study Start Date : February 2014
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Pre- BTX-A injection
Female patients with confirmed diagnosis of Multiple Sclerosis referred to our Neurourology clinic with neurogenic lower urinary tract dysfunction prior to receiving intradetrusor injection of Botulinum Toxin-A.
Post- BTX-A injection
Female patients with confirmed diagnosis of Multiple Sclerosis referred to our Neurourology clinic with neurogenic lower urinary tract dysfunction who receive intradetrusor Botulinum Toxin-A.
Drug: Intradetrusor injection of Botulinum Toxin-A
Using cystoscopy, Botulinum Toxin-A is injected into the bladder.
Other Name: OnabotulinumtoxinA, Botox®




Primary Outcome Measures :
  1. Blood Oxygen Level Dependent (BOLD) Signals in brain [ Time Frame: 2 months ]
    During fMRI measurements BOLD signal intensity in regions of interest will be measured at baseline and will be compared to the signals 6 weeks following the injection of BotulinumtoxinA, these signals may be increased or decreased.


Secondary Outcome Measures :
  1. Urodynamic study data [ Time Frame: 2 months ]
    The urodynamic data will be correlated with the functional MRI data. Neurogenic Detrusor Overactivity will be correlated to BOLD signal activation at regions of interest.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Female subjects diagnosed with Multiple Sclerosis and lower urinary tract symptoms who are refractory to conservative management for neurogenic detrusor overactivity.
Criteria

Inclusion Criteria:

  • Patients with clinical diagnosis of neurogenic bladder.
  • History of any neurologic illness or injury (including but not limited to spinal cord injury, Multiple Sclerosis, spina bifida, Parkinson's, major spine surgery).
  • 18 years or older.
  • Female patients.

Exclusion Criteria:

  • Male
  • History of any incontinence surgery (sling, MMK, Burch).
  • History of any lower urinary tract surgery or manipulation (urethral dilation).
  • Positive urine pregnancy test at enrollment .

Information from the National Library of Medicine

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): NCT03033355


Contacts
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Contact: Rashmi Pande, BDS, MS 713-363-9154 rpande@houstonmethodist.org

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Rashmi Pande, BDS, MS, CCRP    713-363-9154    rpande@houstonmethodist.org   
Principal Investigator: Rose Khavari, MD         
Sponsors and Collaborators
Rose Khavari, M.D.
The Methodist Hospital System
Investigators
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Principal Investigator: Rose Khavari, MD The Methodist Hospital System

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Responsible Party: Rose Khavari, M.D., Sponsor-Investigator/Principal Investigator, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT03033355     History of Changes
Other Study ID Numbers: Pro00010110
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rose Khavari, M.D., The Methodist Hospital System:
Neurogenic Bladder, Detrusor Overactivity, Botox, fMRI, neurogenic detrusor overactivity

Additional relevant MeSH terms:
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Sclerosis
Multiple Sclerosis
Lower Urinary Tract Symptoms
Urinary Bladder, Neurogenic
Urinary Incontinence, Urge
Urinary Bladder, Overactive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Urological Manifestations
Signs and Symptoms
Neurologic Manifestations
Urinary Bladder Diseases
Urologic Diseases
Urinary Incontinence
Urination Disorders
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents