Refractory Urge Incontinence and Botox Injections

This study has been terminated.
(higher than anticipated rate of increased post-void residual in subjects who received botulinum toxin A injection)
Sponsor:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00373789
First received: September 6, 2006
Last updated: January 9, 2011
Last verified: October 2010
  Purpose

The purpose of this study is to see whether Botox A (injected into the bladder muscle) can improve symptoms of urge incontinence that has not improved with usual medical treatments.


Condition Intervention Phase
Urinary Incontinence
Detrusor Overactivity
Urinary Urgency
Urge Urinary Incontinence
Drug: Botulinum Toxin A, bladder detrusor muscle injection
Drug: Vehicle saline as placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Refractory Urge Incontinence and Botox Injections

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Time to recurrence of detrusor overactivity incontinence symptoms [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To allow sufficient time for the onset of action of botulinum toxin A, the earliest outcome measurement was 60 days after injection. Failure was defined as a patient global impression of improvement (PGI-I) score of 4 or greater, the commencement of any new treatment at any time after the first injection or increased intensity of previously established treatment for DOI.


Secondary Outcome Measures:
  • Change in incontinence episode frequency by bladder diary [ Time Frame: At 12 mos after first injection., but no less than 1 mo after second injection ] [ Designated as safety issue: No ]
    based on the 3-day bladder diary completed pre-intervention and at 4 weeks post injection. A successful within-subject outcome will be defined as >75% reduction in the frequency of urge incontinence episodes compared to the baseline frequency.

  • Incontinence-related and health-related quality of life [ Time Frame: At 12 mos after first injection, but no less than 1 mo after second injection. ] [ Designated as safety issue: No ]
    measured by the Urinary Distress Inventory subscale of the PFDI/PFIQ, the PISQ, and SF-36 administered at 4 weeks after the initial injection and either prior to any re-treatment or at the completion of study participation, whichever is earlier.

  • Voiding dysfunction requiring catheterization [ Time Frame: throughout 12-month study ] [ Designated as safety issue: Yes ]

Enrollment: 87
Study Start Date: June 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Botox A
up to two injections of 200 Units of intra-detrusor Botulinum Toxin A , which must be separated by at least eight weeks and no more than 52 weeks
Drug: Botulinum Toxin A, bladder detrusor muscle injection
200 U provided as a total of 6 cc of the masked substance into approximately 15 to 20 different detrusor muscle sites under direct visualization. Injections will be spread out to equally cover the entire dome of the bladder, but spare the bladder trigone and ureteral orifices.
Other Name: Botox
Placebo Comparator: Placebo
up to two injections of inactive injection (carrier saline), which must be separated by at least eight weeks and no more than 52 weeks
Drug: Vehicle saline as placebo
A total of 6 cc of the masked substance into approximately 15 to 20 different detrusor muscle sites under direct visualization. Injections will be spread out to equally cover the entire dome of the bladder, but spare the bladder trigone and ureteral orifices

Detailed Description:

Women who suffer with urge incontinence may not get relief with usual medical treatment (such as medications or behavioral techniques). We plan to enroll women with refractory urge incontinence in centers across the US. Study participants will undergo cystoscopy (telescope look into the bladder) and injection of either Botox A or placebo. If symptoms are not adequately relieved, subjects participants will receive a second injection that is Botox A. Participants are interviewed monthly by study personnel to determine symptoms and health status.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult women
  • Detrusor overactivity incontinence confirmed by urodynamic testing
  • Symptoms refractory to standard first- and second-line treatments
  • 6 or more urge incontinence episodes on 3-day bladder diary
  • Normal neurological examination

Exclusion Criteria:

  • Urinary retention
  • Allergy to Botox (Botulinum Toxin A)
  • Previous bladder treatment with Botox (Botulinum Toxin A) in the past year
  • Pregnancy or planning pregnancy within next year
  • Neurologic disease with impaired neurotransmission
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373789

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35249
United States, California
USCD Medical Center
La Jolla, California, United States, 92037
Kaiser Permanente
San Diego, California, United States, 92120
United States, Illinois
Loyola University
Maywood, Illinois, United States, 60153
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Texas
UT Southwestern
Dallas, Texas, United States, 35249
United States, Utah
Univeristy of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Investigators
Study Chair: Linda Brubaker, MD Loyola University
  More Information

Additional Information:
Publications:
Responsible Party: Susan Meikle, MD, NICHD
ClinicalTrials.gov Identifier: NCT00373789     History of Changes
Other Study ID Numbers: PFDN 12
Study First Received: September 6, 2006
Last Updated: January 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Botulinum Toxin A
Urinary Incontinence
Detrusor Overactivity

Additional relevant MeSH terms:
Urinary Incontinence
Urinary Incontinence, Urge
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Botulinum Toxins, Type A
Botulinum Toxins
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014