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Botulin-A Toxin/Dimethyl Sulfoxide Bladder Instillations for Treatment of Voiding Dysfunction Secondary to Detrusor Hyperreflexia and Detrusor Instability in Women

Phase 1
18 Years
Not Enrolling
Overactive Bladder, Detrusor Instability, Detrusor Hyperreflexia of Bladder

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Trial Information

Botulin-A Toxin/Dimethyl Sulfoxide Bladder Instillations for Treatment of Voiding Dysfunction Secondary to Detrusor Hyperreflexia and Detrusor Instability in Women


To date, the standard treatment for overactive bladder (including detrusor hyperreflexia and
detrusor overactivity) consists of oral anticholenergic medications that can have
troublesome side effects and variable efficacy. What's more, patients failing
pharmacological therapy must either live with their malady or undergo open surgery that is
irreversible and carries a prolonged convalescence. The fact remains however that treatment
for overactive bladder is necessary to help maintain quality of life and prevent upper
urinary tract deterioration. In recent years, cystoscopic-guided injection of Botulinum-A
toxin has been used as a novel method of addressing detrusor hyperreflexia and overactivity
by blocking acetylcholine transmission at the bladder. The obvious benefits of a more
targeted therapy notwithstanding, this method requires the use of a cystoscope, needle
delivery of the agent through approximately 30 separate injection sites and either regional
or topical intravesical anesthesia for peri-operative pain control. Clearly, the
identification of less invasive and more cost effective means of delivering the beneficial
effects of Botulinum-A toxin to the bladder muscle has the potential to enhance the overall
appeal of this treatment method.


The primary objective of this pilot study is to evaluate the safety and efficacy of direct
instillations of Botulinum-A toxin/DMSO into the bladder via a catheter system as a means of
treating women with symptoms of overactive bladder and secondary urinary incontinence. In
doing so, we will focus on estimating the percentage of women who experience an improvement
in their urinary incontinence symptoms at one month and three months following this novel
instillation technique.

Study Design:

We are proposing a single center, Phase II pilot study for this investigation. In this
proposal, 25 sterile women between 18-90 years of age with urodynamic evidence of detrusor
overactivity, hyperreflexia or symptoms of overactive bladder syndrome who lack evidence of
infection and stress incontinence will be offered bladder instillation of Botulinum-A toxin
with DMSO as a carrier agent if they have failed anticholinergic medications or cannot
tolerate the pharmacological side effects. We will use two validated measurement tools for
determining urinary incontinence severity. These measurement tools will be administered to
each women at baseline and then again at one month and three-month follow-up time points.
Our analysis will also focus on identifying and describing adverse events among these women
and estimating the percentage of women that experience a successful improvement in their
urinary incontinence symptoms.

Study Duration:

Patients will sign an informed consent and be screened for eligibility. Once determined
eligible for the study, each patient will be scheduled for baseline evaluation and
instillation of Botox/DMSO. Patients will be then followed up at one month and three
months. Patients will be removed from the study if they withdraw consent, experience one of
the study stopping criteria (in which case the entire study will stop) or when they complete
the final follow-up evaluation at three-months.

Inclusion Criteria:

1. Female patient aged 18 years or older

2. Patient with a history of stress urinary incontinence for at least 12 months

3. Patient with Intrinsic Sphincter Deficiency who demonstrate an abdominal leak point
pressure of less than 100 cm of water on urodynamic evaluation

4. Patient with urinary incontinence verified by the Provocation test: a mean urinary
leakage of 10 g on screening and baseline visits

5. Patient with positive stress test and/or urodynamic stress incontinence

6. Patient who has failed prior non-invasive treatment (e.g. behavior modification,
pelvic floor exercises, biofeedback, electrical stimulation and/or drug therapy)

7. Patient with negative Contigen skin test during screening.

8. Patient who is mentally competent with the ability to understand and comply with the
requirements of the study

9. Patient who agrees to be available for the follow-up evaluations as required by the

10. Patient who has given signed informed consent

Exclusion Criteria:

1. Patient with Q-tip angle greater than 30 degrees

2. Patient with Functional Bladder capacity <200 ml as recorded in the baseline Bladder

3. Patient with Post-Void Residual Urine (PVRU) greater than 100 ml on repeated
measures. (Patient with a single PVRU of >100 ml and followed by two consecutive PVRU
measurements of <100 ml may be included in the study)

4. Patient with vesicoureteral reflux, interstitial cystitis, genitourinary fistulae

5. Patient with predominant urge incontinence

6. Patient with detrusor overactivity on filling cystometry

7. Patient with pelvic organ prolapse stage III or IV, i.e. the most distal part of the
prolapse protruding more than 1 cm beyond the hymen (>+1), at straining

8. Patient with urinary incontinence due to neurological disease that is known to affect
urinary tract infection

9. Patient with univestigated hematuria

10. Patient with genitourinary malignancies

11. Patient on current medication for stress urinary incontinence, such as
alpha-adrenergic agonists or duloxetine, within three weeks prior to completing the
baseline Bladder Diary (estrogen therapy on a stable dose for at least two months
prior to study start is allowed)

12. Patient who has had bulking therapy for stress urinary incontinence

13. Patient with ongoing complications of prior anti-incontinence surgery

14. Patient who is pregnant, lactating, or planning to become pregnant within the study

15. Patient who has received pelvic radiation

16. Patient with any condition, which could lead to significant postoperative
complications, including current infection and uncontrolled diabetes.

17. Patient who is morbidly obese (defined as BMI > 32 Kg/m2)

18. Patient who is bedridden, institutionalized or in such physical condition that she
cannot move to the closest bathroom without assistance from another person

19. Patient with current or acute urinary tract infection, including cystitis or
urethritis. (Patient with such infections should be treated with antibiotics, with
subsequent urinalysis tests confirming the absence of such infection before study

20. Patient with any condition that would preclude treatment due to contraindications
and/or warnings in the study product's labeling

21. Patient on concomitant medication with anticoagulant properties (e.g., Warfarin,
Heparin, Aspirin, NSAIDs, except for cox-2 inhibitors) within two weeks prior to

22. Patient on immunomodulatory therapy (suppressive or stimulatory)

23. Patient with a known allergy to bovine collagen

24. Patient with known lidocaine hypersensitivity or hypersensitivity to any anesthetics
to be used during the treatment session/surgical procedure

25. Patient with a concurrent use of another study product within two weeks prior to
study start, or who concurrently participate in any other clinical study

26. Any disease that in the opinion of the Investigator would make the patient unsuitable
for the study

27. Patient with a life expectancy of less than 12 months

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Success is any women whose quantitative symptoms score on either the Blaivas - Groutz score or the IUSS score move from the 'severe' or 'moderate' category to the 'mild' category or from the 'mild' category to the 'none' category.

Outcome Time Frame:

1 month and 3 month post treatment

Safety Issue:


Principal Investigator

Steven Petrou, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic



Study ID:




Start Date:

March 2006

Completion Date:

May 2008

Related Keywords:

  • Overactive Bladder
  • Detrusor Instability
  • Detrusor Hyperreflexia of Bladder
  • Reflex, Abnormal
  • Urinary Bladder, Overactive



Mayo Clinic JacksonvilleJacksonville, Florida  32224