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OnabotulinumtoxinA (onaBoNT-A) Versus Oral Oxybutynin ER in Spinal Cord Injured Veterans With Neurogenic Detrusor Overactivity

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Baylor College of Medicine
Sponsor:
Information provided by (Responsible Party):
Christopher Patrick Smith, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01050114
First received: January 11, 2010
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

Overactive bladder is a condition associated with symptoms of feeling the urge to urinate, urinating often, and may or may not be accompanied by leakage of urine. A patient who has a spinal cord injury (SCI) often suffers from an overactive bladder which often leads to urinary incontinence (UI - an unwanted leakage of urine).

Current treatment for incontinence in some SCI patients is clean intermittent self-catheterization (CIC). This is a procedure done by inserting a catheter (a soft, hollow tube) into the urethra into the bladder in order to empty the bladder. However, CIC can be associated with infection, which can make the urinary incontinence worse and can lead to kidney damage. There are drugs that may help with the incontinence but they are likely to cause dry mouth, constipation, and blurred vision.

OnaBoNT-A bladder injections have been studied in clinical research trials. The results have shown an improvement in urinary symptoms by reducing how often urine leakage occurs and by increasing the amount of urine the bladder can hold.

This purpose of this clinical trial is to see if onaBoNT-A is safe and effective when injected into the bladder for the treatment of UI and if it works better than a drug that is taken by mouth. A second purpose of the study is to perform research tests on the urine samples provided by the volunteers. Urine presents a rich source of information for bladder diseases and the biomarkers (the chemical make-up of the urine cells) will be examined to learn if there are yet undiscovered reasons for urinary diseases. These tests would be very beneficial because the results would lead to better treatment of the urinary diseases.

Volunteers will be randomized using a blocked randomization approach designed by the statistician and implemented by the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) Research Pharmacy to either: ARM 1: onaBoNT-A 200 U bladder injection and placebo oral capsule daily or ARM 2: Placebo bladder injection (saline) and oxybutynin ER 15mg capsule daily. Subjects will be randomized into one of the two treatment arms, using a block size of 4. The order in which the treatments are assigned in each block is randomized and this process is repeated for consecutive blocks of subjects until all subjects are randomized. This process ensures that after every fourth randomized subject, the number of subjects in each treatment group is equal.

The treatments are onaBoNT-A bladder injection and a placebo oral capsule once a day or placebo bladder injection and oxybutynin ER (like Ditropan) capsule once a day. Placebo contains no active medicine. Participation in this study will be about 6-7 months and involve 5 visits to the clinic. The risks of bladder onaBoNT-A injection are very small but include bleeding, infection, and the rare risk of spread of onaBoNT-A to other muscles causing weakness. Side effects of oxybutynin ER include dry mouth, constipation, and blurred vision. The potential benefits to the volunteer include improvement in the urinary incontinence symptoms, decrease in the number of required catheterizations, and an ease of the financial burden of buying protective garments.


Condition Intervention Phase
Neurogenic Detrusor Overactivity
Drug: onabotulinumtoxin A
Drug: Oxybutynin ER
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized Study of the Safety and Efficacy of OnabotulinumtoxinA (OnaBoNT-A) Versus Oral Oxybutynin in Spinal Cord Injured Veterans With Neurogenic Detrusor Overactivity (Protocol Number 11-09-10-04)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Primary endpoint [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The primary endpoint is the reduction in mean weekly incontinent episodes in the onaBoNT-A treated group compared to the oxybutynin treated group at 12 weeks.


Secondary Outcome Measures:
  • The utility of urinary inflammatory markers as statistically significant predictors of treatment response. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: August 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
ARM 1: onaBoNT-A injection + placebo oral capsule
onaBoNT-A 200 U (treatment 1)/ onaBoNT-A 200 U (treatment 2)/ onaBoNT-A 200 U (treatment 3) and placebo oral capsule daily
Drug: onabotulinumtoxin A

onaBoNT-A will be the active formulation. Each vial of onaBoNT-A Purified Neurotoxin Complex, Formulation No. 9060X, contains: 100 units (U) of Clostridium botulinum toxin type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. One U corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice. A 0.9% sterile saline (without preservative) for injection will be used as diluent for onaBoNT-A.

Each treatment session will be administered as 20 injections each of 1 mL (10U/ml), evenly distributed into the bladder.

Other Names:
  • onaBoNT-A
  • BOTOX(R)
ARM 2: Placebo injection + oxybutynin ER
Placebo injection (treatment 1)/ onaBoNT-A 200 U (treatment 2)/ onaBoNT-A 200 U (treatment 3) and oxybutynin ER 10 mg capsule daily
Drug: Oxybutynin ER
Oxybutynin ER in a 15 mg capsule will be taken daily for the course of the study.
Other Names:
  • Ditropan XL
  • Urotrol
  • Oxytrol

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male or female, aged 18 to 80 years old, weighing 110 pounds or more.
  • a veteran of the United States military service who has suffered a spinal cord injury.
  • urinary incontinence as a result of neurogenic detrusor overactivity for a period of at least 3 months prior to screening as a result of spinal cord injury
  • must have a stable neurological injury occurring at least 6 months or more.
  • has detrusor overactivity demonstrated during the screening period or within 6 months of screening if patient is off antimuscarinic/ anticholinergic drugs at the time of urodynamic testing.
  • has a negative pregnancy result if female and of childbearing potential.

The following criteria are also required for entry into the study at Randomization/Day 1:

  • experiences at least 14 episodes or more of urinary incontinence per week with no more than 2 incontinent-free days.
  • currently uses or is willing to use clean intermittent catheterization (CIC) to empty the bladder (indwelling catheter is not permitted).
  • Volunteers with a negative urine culture result must take an antibiotic medication for 3 days immediately prior to Randomization/Day 1 and agree to continue antibiotic medication for at least 3 days following treatment. Volunteers with a positive urine culture result indicating urinary tract infection (UTI), must take an antibiotic to which the identified organism is sensitive for at least 3 days immediately prior to Randomization/Day 1, on Randomization/Day 1, and continue for 3 days following the procedure (or longer as needed).

Exclusion Criteria:

  • has history or evidence of any pelvic or urological abnormalities including but not limited to the following:

    1. elevated serum creatinine more than 2 times the upper limit of normal (reference range)
    2. current or history of hematuria, 1) if the hematuria is determined to be a pathologic condition or 2) is uninvestigated
    3. interstitial cystitis in the opinion of the investigator bladder stones within 6 months of screening
    4. surgery or bladder disease other than detrusor overactivity that may impact bladder function with the exception of surgeries for bladder stones (more than 6 months) and stress incontinence, uterine prolapse, rectocele, or cystocele (more than1year) from screening.
  • has had previous or current botulinum toxin therapy within 3 months.
  • has been immunized for any botulinum toxin serotype.
  • discontinued anticholinergic medication for overactive bladder less than 14 days prior to Randomization/Day 1.
  • has a history or current diagnosis of bladder cancer.
  • male with previous or current diagnosis of prostate cancer or has a Prostate Specific Antigen (PSA) level greater than 10.0 ng/mL.
  • has 24 hour total volume voided more than 3000 mL of urine
  • has a post void residual volume above 200 mL.
  • has an active genital infection, other than genital warts, either concurrently or within 4 weeks prior to screening.
  • uses any anti-platelet or anticoagulant therapy or is using medications with anticoagulative effects within 3 days prior to treatment.
  • has hemophilia or other clotting factor deficiencies or disorders that cause bleeding diatheses.
  • has had concurrent treatment or treatment within 6 months of Randomization/Day 1 with capsaicin or resiniferatoxin.
  • currently using or plans to use an implanted or non-implantable electrostimulation/ neuromodulation device for treatment of overactive bladder.
  • has a known allergy or sensitivity to any components of the study medication, anesthetics or antibiotics or any other products associated with the treatment and general study procedures.
  • has any medical condition that may put the volunteer at increased risk with exposure to onaBoNT-A including diagnosed myasthenia gravis, Eaton-Lambert syndrome or amyotrophic lateral sclerosis.
  • female and pregnant, nursing or planning a pregnancy during the study, or of childbearing potential and unable or unwilling to use a reliable form of contraception during the study.
  • currently or has previously participated in another therapeutic drug or device study within 30 days of screening.
  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: NCT01050114

Contacts
Contact: Sebrina Tello 713-798-8106 stello@bcm.edu

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Sebrina Tello    713-798-8106    stello@bcm.edu   
Michael E. DeBakey Veterans Affairs Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Sebrina Tello, CCRP    713-791-1414 ext 5326    Sebrina.Tello@va.gov   
Sponsors and Collaborators
Christopher Patrick Smith
Investigators
Study Director: Christopher P. Smith, MD Baylor College of Medicine
  More Information

Publications:
Responsible Party: Christopher Patrick Smith, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01050114     History of Changes
Other Study ID Numbers: 11-09-10-04 (BCM H-26296), H-26296
Study First Received: January 11, 2010
Last Updated: July 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Botulinum Toxin
Oxybutynin
Overactive Bladder
Spinal Cord Injury
Urinary Incontinence
Nerve Growth Factor
Urine Biomarkers

Additional relevant MeSH terms:
Botulinum Toxins, Type A
Oxybutynin
Autonomic Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neuromuscular Agents
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Urological Agents

ClinicalTrials.gov processed this record on November 19, 2014