Intravesical Injection of Botulinum Toxin A Versus Saline for Neurogenic Detrusor Overactivity

Prospective Randomized Double-blind Trial of Intravesical Injection of Botulinum Toxin A Versus Saline for Neurogenic Detrusor Overactivity and Urinary Incontinence Related to Spinal Cord Injury or Multiple Sclerosis

This is a prospective, multicentre (7 sites), randomized, double-blind, study comparing intravesical injection of BOTOX to placebo in 56 subjects with NDO secondary to spinal cord injury or multiple sclerosis. Study subjects will be randomized to one of the following two treatment groups:

Group 1 n=28 BOTOX - 300U Group 2 n=28 Placebo BOTOX (saline)

All study subjects will receive one injection cycle (BOTOX 300U or Placebo) at Visit 2 (Treatment, Day 0) as per Supplement III. The study duration is approximately 61 weeks and consists of a Pre-Treatment Evaluation, a Treatment/Randomization Visit (Visit 2, Day 0), Telephone Follow-ups at 1, 3 and 4 weeks post-treatment, and Follow-up Visits at 6, 24 and 36 weeks (Visits 3 to 5). At Week 36, subjects will be offered open-label BOTOX 300U and will be followed for an additional 6 months, returning for evaluations at Weeks 48 and 60.

Study Overview

• Status: Completed
• Conditions: Neurogenic Detrusor Overactivity
• Intervention / Treatment: Drug: Botulinum toxin A

Detailed Description

This is a prospective, multicentre (7 sites), randomized, double-blind, study comparing intravesical injection of BOTOX to placebo in 56 subjects with NDO secondary to spinal cord injury or multiple sclerosis. Study subjects will be randomized to one of the following two treatment groups:

Group 1 n=28 BOTOX - 300U Group 2 n=28 Placebo BOTOX (saline) All study subjects will receive one injection cycle (BOTOX 300U or Placebo) at Visit 2 (Treatment, Day 0) as per Supplement III. The study duration is approximately 61 weeks and consists of a Pre-Treatment Evaluation, a Treatment/Randomization Visit (Visit 2, Day 0), Telephone Follow-ups at 1, 3 and 4 weeks post-treatment, and Follow-up Visits at 6, 24 and 36 weeks (Visits 3 to 5). At Week 36, subjects will be offered open-label BOTOX 300U and will be followed for an additional 6 months, returning for evaluations at Weeks 48 and 60.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Outpatient, male or female subjects, of any race, between 18 and 75 years of age. Female subjects of childbearing potential must have a negative urine pregnancy test result on the day of Treatment (Visit 2) and practice a reliable method of contraception.
2. Subjects with a neurogenic bladder and detrusor overactivity secondary to either a spinal cord injury or multiple sclerosis.
3. Subjects with urinary incontinence (minimum of one occurrence per day) despite current treatment.
4. Subjects with serum creatinine within normal limits and normal renal function.
5. Subjects on a stable dose (minimum one month) of concomitant medication for NDO.
6. Subjects able to understand the requirements of the study, including completing questionnaires and signing Informed Consent.

Exclusion Criteria

1. Female subjects who are pregnant (positive urine pregnancy test), are planning to become pregnant during the study period, have an infant they are breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control.
2. Subjects with a history of transurethral sphincterotomy, bladder neck or prostatic resection, previous bladder surgery including myomectomy or augmentation cystoplasty.
3. Subjects with chronic indwelling catheters.
4. Subjects with any medical condition that may increase their risk of exposure to botulinum toxin including diagnosed Myasthenia Gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis or any other disease that might interfere with neuromuscular function.
5. Subjects with an allergy or sensitivity to any component of BOTOX® (Section 5.2).
6. Subjects unable to discontinue any agents that might interfere with neuromuscular function (i.e., aminoglycoside antibiotics, curare-like agents, etc.).
7. Subjects with, in the opinion of the Investigator, unstable stable multiple sclerosis.
8. Subjects with known, uncontrolled systemic disease.
9. Subjects with evidence of recent alcohol/drug abuse.
10. Subjects who, in the opinion of the Investigator, have a significant condition or situation that may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
11. Subjects with a history of poor cooperation, non-compliance, or unreliability.
12. Subjects currently participating in an investigational drug study or who have participated in an investigational drug study within 30 days of the Baseline Visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum toxin A; Botulinum toxin A 300U diluted with sterile saline (1 ml per injection site) and injected into 30 sites of the bladder, sparing the trigone.	Drug: Botulinum toxin A; Comparison of intra-detrusor injection of 300U of Botulinum toxin A versus placebo for effect on neurogenic detrusor overactivity and urinary incontinence.; Other Names: Botox
Placebo Comparator: Placebo; Sterile saline 30 cc injected into 30 sites in the bladder, sparing the trigone.	Drug: Botulinum toxin A; Comparison of intra-detrusor injection of 300U of Botulinum toxin A versus placebo for effect on neurogenic detrusor overactivity and urinary incontinence.; Other Names: Botox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Frequency of Incontinence Episodes over 3 days (3-Day Voiding Diary)	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Maximum Detrusor Pressure During Filling;Volume at Maximum Detrusor Pressure During Filling at 6 Wks;Volume at Maximum Detrusor Pressure During Filling other than at 6 Wks;Reflex Detrusor Volume at First Contraction; Maximal Bladder Capacity;Frequency of micturition; Bladder Compliance;ICIQ,DBICI,I-QOL Incontinence intervals, number of pads used, amount leaked, degree of urgency Intermittent Catheterizations;Urine volume obtained during catheterization Timing and reduction or cessation of anticholinergic medication	36 weeks

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: ethica Clinical Research Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 22, 2010
• First Submitted That Met QC Criteria: March 22, 2010
• First Posted (Estimate): March 24, 2010

Study Record Updates

• Last Update Posted (Estimate): March 24, 2010
• Last Update Submitted That Met QC Criteria: March 22, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Bladder; Spinal; Injury; Neurogenic; Detrusor; Overactive; Overactivity; Cord
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 0922006