Intravesicular Onabotulinumtoxin A in Interstitial Cystitis

The Impact of Injection Location on the Efficacy of Intravesicular Onabotulinumtoxin A in Interstitial Cystitis--Phase 4

The purpose of this research study is to identify the optimal usage of Onabotulinumtoxin A in interstitial cystitis. Onabotulinumtoxin A, more commonly known by the trade name Botox®, is a medication that comes from the bacteria Clostridium botulinum. It works by blocking the release of the neurotransmitter acetylcholine(a chemical messenger that carries signals between nerve cells and other cells in the body). Blocking that neurotransmitter results in decreased muscle activity.

Study Overview

• Status: Completed
• Conditions: Interstitial Cystitis
• Intervention / Treatment: Drug: Onabotulinumtoxin A; Procedure: injections upper aspect of trigone of urinary bladder; Procedure: injections on posterior bladder wall excluding the trigone

Detailed Description

The purpose of this study is to evaluate the efficacy of intravesicular Onabotulinumtoxin A injections for the treatment of interstitial cystitis (IC). Specifically, we hypothesize that trigonal Onabotulinumtoxin A injections is an effective treatment for IC and will result in more subjective and objective symptom relief than posterior wall Onabotulinumtoxin A injections.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Adult females between the ages of 18 and 80 inclusive
2. Patients being treated for IC who are refractory to conservative management and oral therapy.
3. willing and able to initiate catheterization post-treatment

Exclusion Criteria:

1. Any history of bladder cancer, uterine cancer, ovarian cancer, vaginal cancer, urethral diverticulum, spinal cord injury, stroke, Parkinson's disease, multiple sclerosis, spina bifida, cyclophosphamide treatment, radiation treatment to the pelvis, bladder tuberculosis, genital herpes.
2. Currently on or requiring anti-platelet/anti-coagulant concomitant therapy or having been on anti-platelet/ anti-coagulant therapy within the past 3 months
3. Pregnancy. Pregnancy is an absolute contraindication to undergoing these procedures. Thus, as part of their normal pre-operative work up, which is standard of care, pregnancy tests are administered if they are women of child-bearing age, are sexually active, and are within 10 days of the normal menstrual period. If positive, they will be excluded as they will not undergo the procedure.
4. An active urinary tract infection as shown during clean-catch urinalysis at screening visit. Subject may be re-screened if UTI is successfully treated and urinalysis is negative at rescreening.
5. A history of hypersensitivity or allergy to any botulinum toxin preparation
6. A post-void residual (PVR) urine volume >200mL at baseline
7. Treatment with botulinum toxin during the 12 week period prior to the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botox upper aspect trigone; Subjects in the experimental cohort will receive a one time dose of 100 units of Onabotulinumtoxin A diluted in 10 mL of preservative free normal saline and injected in 1.0 mL boluses in a set pattern across the upper aspect of the trigone of the urinary bladder.	Drug: Onabotulinumtoxin A; 100 units of botox spread out among 10 separate injections; Other Names: Botox; Procedure: injections upper aspect of trigone of urinary bladder; We hypothesize that injections into the trigone should be more effective in the treatment of IC than injections elsewhere in the bladder.
Active Comparator: botox periphery of trigone; Each group will receive a total of 100 units of botox spread out among 10 separate injections. Subjects in the control group will have 10 injections made about the periphery of the trigone. The control cohort will receive a one time dose of Onabotulinumtoxin A using the same dilution and number of boluses, but boluses will be administered at random sites on the posterior bladder wall (excluding the trigone).	Drug: Onabotulinumtoxin A; 100 units of botox spread out among 10 separate injections; Other Names: Botox; Procedure: injections on posterior bladder wall excluding the trigone; We hypothesize that injections into the trigone should be more effective in the treatment of IC than injections elsewhere in the bladder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Outcome Will be Assessing the Measurement of Subjective Patient Pain Using the O'Leary-Sant Symptom and Problem Indexes.	The O'Leary-Sant is one questionnaire that assesses the severity of symptoms and the how much of a problem the symptoms cause for the patient and it provides two scores. The scores ranges for the symptoms is 0-20 and for how bothersome the symptoms are, the score range is 0-16. Higher scores for both denotes worse outcomes.	30 and 90 days post treatment
The Primary Outcome Will be Assessing the Measurement of Subjective Patient Pain Using the Pelvic Pain and Urinary Urgency Frequency (PUF) Questionnaire	The PUF questionnaire evaluates symptoms of pain and how much they bother the patient. Two score are given and added together to produce a total score. The score range for symptoms is 0-28 and the range for bother is 0-16. Higher scores denotes worse outcomes.	30 and 90 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient Performance in Uroflowmetry.	Uroflowmetry is a test that measures the volume of urine released from the body, the speed with which it is released, and how long the release takes.	30 days and 90 days post treatment

Other Outcome Measures

Outcome Measure	Time Frame
Secondary Outcomes Will be Assessing Change in Patient Performance in Post Void Residuals.	30 days and 90 days post treatment

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Allergan
• Investigators: Principal Investigator: Robert J Evans, M.D., Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): January 10, 2018
• Study Completion (Actual): January 10, 2018

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: November 18, 2014
• First Posted (Estimate): November 21, 2014

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: women; interstitial cystitis; bladder pain syndrome; botox; onabotulinum toxin A
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Cystitis; Cystitis, Interstitial; 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, Type A; abobotulinumtoxinA
• Other Study ID Numbers: IRB00026734

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No