Botox for Overactive Bladder

Overseen By Alyssa McDonald

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Northwestern University

Disqualifiers: Allergy to OnabotulinumtoxinA, Bladder cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate (at time of HoLEP)

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called OnabotulinumtoxinA (commonly known as Botox), injected into the bladder, to determine its effectiveness for men with overactive bladder symptoms. These symptoms include frequent urination, waking at night to urinate, a sudden urge to go, or urine leakage. The trial aims to assess the safety and effectiveness of this treatment when administered during a specific prostate procedure (HoLEP). Men undergoing HoLEP who experience these bladder symptoms may be suitable candidates for the trial. Participants should be able to complete forms and consent to join the study.

As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking medical advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that OnabotulinumtoxinA is likely to be safe for humans?

Research has shown that OnabotulinumtoxinA, commonly known as Botox, is generally safe for treating symptoms of an overactive bladder. Studies have found that patients receiving Botox injections in the bladder might experience some side effects. The most common side effects reported within 12 weeks include urinary tract infections (UTIs) and painful urination. About 18% of patients treated with Botox had UTIs, compared to 6% who did not receive it.

Research also indicates that Botox injections can help reduce the number of daily episodes of urinary incontinence, which is the uncontrolled leakage of urine, in patients with an overactive bladder. While there are some risks, many patients find the benefits helpful.

The FDA has approved Botox for treating overactive bladder in certain cases, indicating a level of established safety. However, anyone considering joining a clinical trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for overactive bladder?

Most treatments for overactive bladder, like anticholinergic medications, work by relaxing the bladder muscles to reduce urgency and frequency. But OnabotulinumtoxinA, commonly known as Botox, works differently by blocking nerve signals that trigger bladder muscle contractions. This unique mechanism can offer relief for those who haven't responded well to traditional medications. Researchers are excited because Botox can be directly injected into the bladder, potentially providing targeted, longer-lasting effects with fewer systemic side effects than oral medications.

What evidence suggests that OnabotulinumtoxinA might be an effective treatment for overactive bladder?

Research has shown that Botox, administered as an intra-detrusor OnabotulinumtoxinA injection, can reduce symptoms of an overactive bladder. One study found that long-term use of Botox consistently lessened these symptoms and improved patients' quality of life. Another study demonstrated that Botox significantly improved all symptoms of overactive bladder with no known cause and also enhanced patients' quality of life. However, a small number of patients needed a catheter to help empty their bladder because they couldn't fully do so after treatment. Overall, Botox has shown promising results in managing overactive bladder symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Amy Krambeck, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for men aged 18-89 who are undergoing HoLEP surgery and have overactive bladder symptoms, including frequent urination, nighttime urination, urgency, or urge-related incontinence. Participants must be able to understand and fill out questionnaires. Men with allergies to Botox, other surgeries at the same time as HoLEP, prior pelvic radiation or bladder cancer history, decision-making impairments, or active urinary infections cannot join.

Inclusion Criteria

I experience frequent urination, need to urinate at night, sudden urges to urinate, and/or leakage due to urgency.

Willing to sign the Informed Consent Form

Able to read, understand, and complete patient questionnaires

Exclusion Criteria

I currently have a urinary tract infection.

I might need a surgical opening in the perineum during my prostate surgery.

I am having a procedure for kidney stones or another surgery at the same time as my HoLEP.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Intra-detrusor OnabotulinumtoxinA injections are administered at the time of HoLEP

Immediate (at time of HoLEP)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of urinary retention, hematuria, and other complications

3 months

Clinic/telephone follow-up

Extended Follow-up

Long-term monitoring of symptom resolution and efficacy endpoints through patient surveys and clinical assessments

6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• OnabotulinumtoxinA

Trial Overview The study is testing the safety and effectiveness of injecting OnabotulinumtoxinA (Botox) into the bladder muscle during a prostate surgery called HoLEP in men with overactive bladder symptoms. It's a multi-center study where participants are randomly chosen to receive either Botox injections or not during their procedure.

How Is the Trial Designed?

Group I: Intra-detrusor OnabotulinumtoxinA Injection Experimental Treatment 1 Intervention

Injection of intra-detrusor OnabotulinumtoxinA into the bladder will be performed.

Group II: No intra-detrusor OnabotulinumtoxinA Injection Active Control 1 Intervention

Injection of intra-detrusor OnabotulinumtoxinA into the bladder will not be performed.

OnabotulinumtoxinA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Botox for:

• Chronic migraine
• Involuntary muscle contractions or twitching
• Excessive sweating
• Increased saliva
• Overactive bladder
• Urinary incontinence
• Facial wrinkles
• Cervical dystonia
• Upper limb spasticity
• Lower limb spasticity

Approved in European Union as Botox for:

• Blepharospasm
• Strabismus
• Axillary hyperhidrosis
• Cervical dystonia
• Upper limb spasticity
• Lower limb spasticity
• Overactive bladder
• Urinary incontinence
• Facial wrinkles

Approved in Canada as Botox for:

• Chronic migraine
• Involuntary muscle contractions or twitching
• Excessive sweating
• Increased saliva
• Overactive bladder
• Urinary incontinence
• Facial wrinkles
• Cervical dystonia
• Upper limb spasticity
• Lower limb spasticity

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

Published Research Related to This Trial

In a study of 686 Korean patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO) or overactive bladder (OAB), onabotulinumtoxinA significantly reduced UI symptoms, with 64.9% of NDO patients and 47.3% of OAB patients showing a meaningful improvement of over 5 points on the ICIQ-SF scale.

The treatment was found to be safe, with only a small percentage of patients experiencing adverse drug reactions (5.6% for NDO and 3.2% for OAB), primarily related to urinary tract issues, indicating a favorable risk-benefit profile for onabotulinumtoxinA in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Korean Postmarketing Study Assessing the Effectiveness of OnabotulinumtoxinA for the Treatment of Neurogenic Detrusor Overactivity or Idiopathic Overactive Bladder Using a Validated Patient-Reported Outcome Measure. Ko, KJ., Jenkins, B., Patel, A., et al.[2020]

In a study of 290 patients receiving intravesical onabotulinumtoxinA (BoNT-A) for overactive bladder, common adverse events included acute urinary retention (8.3%) and urinary tract infections (15.2%) within 3 months post-treatment.

Predictive factors for these adverse events included being male, older than 61 years, having a low maximum flow rate (Qmax), high post-void residual (PVR) volume, and low voiding efficiency, indicating that certain patient characteristics can help identify those at higher risk for complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive factors of adverse events after intravesical suburothelial onabotulinumtoxina injections for overactive bladder syndrome-A real-life practice of 290 cases in a single center. Jiang, YH., Ong, HL., Kuo, HC.[2018]

In a pilot study involving 28 patients with refractory overactive bladder (OAB) after surgery for benign prostatic hyperplasia (BPH), onabotulinumtoxinA (BOTOX) showed significant improvements in quality of life and lower urinary incontinence scores at 6 and 9 months post-treatment.

Patients receiving onabotulinumtoxinA experienced a reduction in urinary frequency from 11 to 8 voids per day, while the placebo group showed no change, indicating potential efficacy in managing OAB symptoms, although larger studies are needed for confirmation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo controlled pilot study of intradetrusor injections of onabotulinumtoxinA for the treatment of refractory overactive bladder persisting following surgical management of benign prostatic hyperplasia. Chughtai, B., Dunphy, C., Lee, R., et al.[2018]

Botulinum toxin-A significantly improves symptoms of idiopathic overactive bladder (OAB), including reduced urinary frequency and incontinence episodes, based on a review of 12 randomized controlled trials involving 1,020 participants.

While effective, botulinum toxin-A is associated with a higher risk of urinary retention and urinary tract infections compared to placebo, suggesting that lower doses may provide a better balance of benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin-A injections for idiopathic overactive bladder: a systematic review and meta-analysis. Cui, Y., Wang, L., Liu, L., et al.[2022]

In a systematic review of 11 randomized controlled trials involving 1008 patients, onabotulinumtoxinA (BOTOX) was found to be significantly more effective than placebo in improving bladder control, symptoms, and quality of life for patients with refractory idiopathic overactive bladder (iOAB).

The treatment was well tolerated, with manageable adverse events such as urinary retention and infections, which did not negatively impact the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Idiopathic overactive bladder and BOTOX(®): Literature review]. Gamé, X., Karsenty, G., Ruffion, A., et al.[2018]

In a study of 207 patients with non-neurogenic overactive bladder, both onabotulinumtoxinA (Botox) and abobotulinumtoxinA (Dysport) showed similar effectiveness in reducing symptoms like daytime frequency and incontinence episodes.

However, abobotulinumtoxinA was associated with a significantly higher rate of urinary retention requiring intermittent self-catheterization (42% vs 23%), indicating that these two treatments are not interchangeable at the doses used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox(®) ) or abobotulinumtoxinA (Dysport(®) ) make a difference? Ravindra, P., Jackson, BL., Parkinson, RJ.[2018]

In a study of 208 women with idiopathic overactive bladder (OAB) treated with 100 U of Botox, older and multiparous women were found to be at a higher risk for urinary retention, particularly those requiring clean intermittent self-catheterization (CISC).

The risk of urinary retention significantly decreased by 2 weeks post-injection, indicating that close monitoring during this period is crucial for OAB patients after receiving Botox treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary retention in female OAB after intravesical Botox injection: who is really at risk? Miotla, P., Cartwright, R., Skorupska, K., et al.[2018]

In a study of 102 women, both those with idiopathic overactive bladder (OAB) and those with de novo OAB after midurethral sling surgery showed significant improvement in symptoms after receiving onabotulinumtoxinA injections, with similar rates of being completely dry (41.5% vs. 38.8%).

The treatment led to a notable reduction in daily voids and incontinence episodes for both groups, with urinary retention occurring in only four patients, indicating that the safety profile of onabotulinumtoxinA is acceptable even in women who have undergone previous surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of botulinum toxin injection in the treatment of de novo OAB symptoms following midurethral sling surgery. Miotla, P., Futyma, K., Cartwright, R., et al.[2018]

In a study involving 97 patients across six urogynecology centers, OnabotulinumtoxinA (Botox) was primarily used as a second-line treatment for idiopathic overactive bladder after previous therapies like tibial or sacral neuromodulation failed, with 70% of first injections adhering to marketing authorization guidelines.

The study highlighted significant variability in diagnostic and treatment practices among centers, indicating a need for greater standardization in the use of Botox for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Botulinium toxin and idiopathic overactive bladder: Multicentric contempory management in Bourgogne]. Schneider, A., Tourlonias, B., Cormier, L., et al.[2019]

In a study of 278 adults receiving onabotulinumtoxin A (BTX-A) for overactive bladder, 35% of men and 17% of women experienced incomplete emptying, with men having 2.4 times higher odds than women.

The study found that 17% of men and 23.5% of women developed urinary tract infections (UTIs) post-injection, with a history of prior UTIs being the strongest predictor for developing a UTI after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incomplete bladder emptying and urinary tract infections after botulinum toxin injection for overactive bladder: Multi-institutional collaboration from the SUFU research network. Reynolds, WS., Suskind, AM., Anger, JT., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10222470/

Retrospective Observational Study of Treatment Patterns ... This retrospective study was aimed at evaluating the treatment pattern and long-term effectiveness of onabotulinumtoxinA injections in clinical practice.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772973723009244

16 year's experience of a Tertiary Centre in the UK 52% of patients were lost to follow-up and 30% are ongoing patients. Recurrent UTIs developed in 23%. Conclusion: Repeated Botox injections appear to be a safe ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27038769/

Final Results of a 3.5-Year Study Conclusions: Long-term onabotulinumtoxinA treatment consistently decreased overactive bladder symptoms and improved quality of life with no new safety signals.

4. botoxone.com botoxone.com/oab/efficacy

Overactive Bladder - Efficacy In clinical trials, 6.5% of patients (36/552) initiated CIC for urinary retention following treatment with BOTOX 100 Units, as compared to 0.4% of patients (2/ ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/nau.25538

Efficacy and safety of onabotulinumtoxinA for the treatment ... OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3649594/

The use of botulinum toxin for the treatment of overactive ... A recent growing body of evidence suggests that intra-detrusor injection of botulinum toxin may have beneficial effects in patients with medication refractory ...

7. botoxone.com botoxone.com/oab/safety

Overactive Bladder - Safety The most frequently reported adverse reactions for overactive bladder occurring within 12 weeks of injection include UTI (BOTOX 18%, placebo 6%); dysuria (BOTOX ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00311376

Safety and Efficacy Study of Botulinum Toxin Type A for the ... The purpose of this study is to assess the safety and effectiveness of botulinum toxin type A in treating overactive bladder in spinal cord injury or multiple ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/103000s5251lbl.pdf

3247784 This label may not be the latest approved by FDA ... Intradetrusor injection of BOTOX is contraindicated in patients with overactive bladder or detrusor overactivity associated with a neurologic condition who have ...

10. mdpi.com mdpi.com/2072-6651/16/11/484

Evaluating the Efficacy and Safety of Botulinum Toxin in ... Our meta-analysis revealed that both BoNT-A 200 U and 100 U were superior to the placebo in reducing daily UI episodes in elderly OAB patients during the 4–6- ...