Botulinum Toxin in the Treatment of Idiopathic Detrusor Overactivity

Efficacy of Peri-trigonal Onabotulinumtoxin Injections in the Treatment of Refractory Idiopathic Detrusor Overactivity (IDO): A Single-blind, Randomised Controlled Trial Comparing Peri-trigonal Injections vs Injection of the Bladder Body.

Overactive Bladder (OAB) is a chronic condition caused by instability of the detrusor or bladder muscle, which gives rise to symptoms of urinary urgency and often urinary incontinence. Idiopathic Detrusor Overactivity (IDO) is a subset of OAB where the cause for the bladder muscle instability is unknown.

OAB is usually treated by conservative measures or with oral medications eg. anticholinergics. Injection of onabotulinum toxin A (onaBoNT-A) into the bladder wall is licenced in the treatment of refractory IDO where oral medications fail. The injected toxin paralyses the bladder by blocking the ability of certain (motor) nerves to communicate with the bladder muscle. As these nerves are mainly concentrated in what is known as the "body" of the bladder this is traditionally where the injections are given.

In addition to its action on motor nerves, onaBoNT-A also affects sensory nerve pathways. Recent studies show that IDO is caused by both motor and sensory nerve dysfunction, therefore injecting the "trigone", a part of the bladder where sensory nerves are particularly dense, may be of clinical benefit. Three studies comparing trigone versus trigone-sparing injection of botulinum toxin in the treatment of IDO have been carried out. One of these indicated a significant benefit in targeting the trigone and the other two did not show any difference.

Our study aims to examine if injection of onaBoNT-A into the trigone alone will provide symptom and functional improvement in patients with IDO by comparing peritrigonal injection of onaBoNT-A with the traditional method of injection which spares the trigone.

Study Overview

• Status: Unknown
• Conditions: Overactive Detrusor
• Intervention / Treatment: Drug: Botulinum toxin injected to bladder body; Drug: Botulinum toxin injected into trigone

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: H D Flood, FRCSI; Email: e_red1@yahoo.co.uk

Study Locations

• Ireland
  • Limerick, Ireland
    • University Hospital of Limerick
    • Contact: H D Flood

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Fulfil ICS criteria for OAB
• Urodynamically proven detrusor instability
• Symptoms lasting >6/12
• Patients must discontinue anticholinergic medication >14 days prior to randomisation and withhold the use of anticholinergics for the duration of the study.
• Patients with mixed incontinence are eligible if their urge symptoms are predominant. These will be instruced to record only episodes of urge urinary incontinence.
• Providing informed consent to participate in the study
• At least 18 years of age

Exclusion Criteria:

• Previous BoNT-A injection within 9 months of randomisation
• History of any neurological condition e.g. MS, Parkinsons, CVA
• Contraindication to BoNT e.g. Myaesthenia gravis
• Urinary tract infection in previous 6/12
• Antimicrobial therapy in previous 6/12
• Previous or current diagnosis of prostate or bladder cancer
• History of treatment with cyclophosphamide
• Radiation cystitis
• Urethral dilatation, cystometrogram, bladder cystoscopy under anaesthetic or a bladder biopsy in previous 3/12
• Augmentation cystoplasty, cystectomy or neurectomy
• Urethral stricture of <12ch
• Pregnancy
• Sexually active women of childbearing potential who are unwilling to use contraceptive measures for the duration of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Botulinum toxin injected to bladder body; arm will receive 100u of onaBoNT-A in 20x1ml aliquots (5u/ml). 20 injections will be given into the bladder wall, sparing the trigone. Injections will be given through all layers of the bladder eg suburothelially and intradetrusor.	Drug: Botulinum toxin injected to bladder body; arm will receive 100u of onaBoNT-A in 20x1ml aliquots (5u/ml). 20 injections will be given into the bladder wall, sparing the trigone. Injections will be given through all layers of the bladder eg suburothelially and intradetrusor. The intervention will be performed under local anaesthetic using a flexible cystoscope.; Other Names: Botox; Botulinum toxin; Onabotulinumtoxin
Active Comparator: Botulinum toxin injected into trigone; Arm B will receive 100u onaBoNT-A injected into 10x1ml suburothelial peri-trigonal sites (aliquot dose 10u/ml).	Drug: Botulinum toxin injected into trigone; Arm B will receive 100u onaBoNT-A injected into 10x1ml suburothelial peri-trigonal sites (aliquot dose 10u/ml). The procedure will be performed under local anaesthetic by flexible cystoscopy.; Other Names: Botox; Botulinum toxin; Onabotulinumtoxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Global Response Assessment	measured at 3 months following intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcomes - 3 day sensation related bladder diary	Three day sensation related bladder diary	measured at 3 months following intervention
IIQ-7 quality of life questionnaire		measured at 3 months following intervention
Treatment tolerability - numerical rating scale (0-10)		measured at 2 weeks following intervention
UDI-6 quality of life questionnaire		measured at 3 months following intervention

Collaborators and Investigators

• Sponsor: Mr HD Flood
• Investigators: Principal Investigator: H D Flood, FRCSI, University Hospital of Limerick

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): January 1, 2014

Study Registration Dates

• First Submitted: November 29, 2013
• First Submitted That Met QC Criteria: December 8, 2013
• First Posted (Estimate): December 12, 2013

Study Record Updates

• Last Update Posted (Estimate): December 12, 2013
• Last Update Submitted That Met QC Criteria: December 8, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• 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: UHL02/2013