Fewer Botox Injections for Urinary Incontinence

Recruiting in Palo Alto (17 mi)

Overseen by Monique Vaughan, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Virginia

Must not be taking: Anticholinergics

Disqualifiers: Neurologic disease, Pregnancy, Bladder malignancy, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The overall objective of this study is to determine if a reduced injection site protocol (5 injection sites) using an equivalent amount of Botox provides comparable relief of Urgency Urinary Incontinence (UUI) symptoms compared to the standard injection site protocol (15-20 injection sites). Our central hypothesis is that the 5-site injection protocol is non-inferior in terms of relief of UUI symptoms compared to the standard injection site protocol, measured by a non-inferior reduction in the number of UUI episodes per day.

Will I have to stop taking my current medications?

If you were on anticholinergic therapy (medications that help reduce bladder spasms) before joining the trial, you need to have a 3-week period without taking them before enrolling. For other medications, the trial protocol does not specify if you need to stop taking them.

What data supports the effectiveness of the drug Botox (OnabotulinumtoxinA) for urinary incontinence?

Research shows that OnabotulinumtoxinA significantly reduces urinary incontinence and improves bladder management in patients with neurogenic detrusor overactivity. It is effective in decreasing urinary symptoms, increasing quality of life, and has mild side effects like urinary tract infections. ^{1 2 3 4 5}

Is onabotulinumtoxinA safe for treating urinary incontinence?

OnabotulinumtoxinA (Botox) is generally considered safe for treating urinary incontinence, but common side effects include urinary tract infections and temporary difficulty urinating. Long-term studies show it is safe and effective for conditions like overactive bladder and neurogenic detrusor overactivity. ^{6 7 8 9 10}

How does this drug differ from other treatments for urinary incontinence?

This drug, onabotulinumtoxinA, is unique because it is injected directly into the bladder wall, providing an alternative to oral medications and surgery for urinary incontinence. It is particularly effective for those who have not responded well to other treatments, and it offers long-lasting relief, although repeat injections are needed to maintain its effects. ^{4 11 12 13 14}

Research Team

Monique Vaughan, MD

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for English-speaking women over 21 with urgency urinary incontinence, who have not had Botox injections for this condition before. They must be willing to possibly use a catheter and follow the study's procedures. Excluded are those with certain medical conditions, previous pelvic surgeries, or untreated UTIs.

Inclusion Criteria

I am a woman aged 21 or older.

Patient or caregiver willing to perform clean intermittent catheterization, or patient willing to have indwelling Foley catheter in the event this would be required

I am willing and able to follow the study's schedule and procedures.

Exclusion Criteria

You are allergic to botulinum toxin A.

I am recommended or planning to have surgery for stress incontinence or pelvic organ prolapse.

You have blood in your urine and have not been checked by a doctor.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive intra-detrusor Botox injections, either 5 or 15 sites, and are monitored post-procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, completing questionnaires at 2 weeks, 3 months, and 6 months post-procedure

6 months

3 visits (phone interviews)

Treatment Details

Interventions

• Botox (Neurotoxin)

Trial Overview The study aims to see if fewer Botox injection sites (5 instead of the standard 15-20) will be just as effective in reducing episodes of urgency urinary incontinence. Participants will receive an equal amount of Botox but at different numbers of injection sites.

Participant Groups

Group I: Experimental Experimental Treatment 1 Intervention

Subjects in this arm will be administered the same amount of Botox in 5 injection sites.

Group II: Controls Active Control 1 Intervention

Subjects in this arm will be administered the standard injection site protocol (15 sites).

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

James E. Ryan

University of Virginia

Chief Executive Officer since 2018

J.D. from Harvard Law School

Nikki Hastings

University of Virginia

Chief Medical Officer since 2018

Ph.D. in Biomedical Engineering from University of Virginia

Findings from Research

Repeat botulinum toxin A (BTX-A) injections can provide sustained improvements in quality of life for patients with neurogenic detrusor overactivity (NDO), particularly for those receiving four or fewer injections, based on a review of 18 studies involving 1533 patients.

The study found a low rate of adverse events associated with repeat BTX-A injections, indicating that the treatment is generally safe; however, quality of life may decline for patients receiving five or more injections, highlighting the need for further research on long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is repeat Botulinum Toxin A injection valuable for neurogenic detrusor overactivity-A systematic review and meta-analysis. Ni, J., Wang, X., Cao, N., et al.[2019]

In a double-blind, placebo-controlled study involving 275 patients with urinary incontinence due to neurogenic detrusor overactivity, onabotulinumtoxinA significantly improved health-related quality of life (HRQoL) as measured by the Incontinence Quality of Life Questionnaire, with meaningful score increases compared to placebo.

Patients receiving onabotulinumtoxinA reported higher treatment satisfaction and a greater achievement of treatment goals at 6 and 12 weeks, indicating its efficacy in managing urinary incontinence compared to placebo, with no significant differences between the two doses tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. Sussman, D., Patel, V., Del Popolo, G., et al.[2018]

OnabotulinumtoxinA (BoNT-A) injections significantly improved lower urinary tract symptoms (LUTS) in 30 men with primary bladder-neck dysfunction, with total symptom scores decreasing from 21.9 at baseline to 7.8 at 2 months, indicating effective symptom relief.

The treatment was found to be safe, with no significant adverse effects or ejaculatory dysfunction reported, although the benefits appeared to diminish over time, suggesting the need for repeated injections for sustained improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder-neck dysfunction: objective and patient-reported outcomes. Sacco, E., Tienforti, D., Bientinesi, R., et al.[2018]

In a study of 17 patients with neurogenic detrusor overactivity, repeated botulinum toxin type A injections were found to be safe, with no systemic side effects reported across 91 injections.

The treatment effectively reduced incontinence episodes to zero and significantly improved bladder capacity and pressure, maintaining these benefits consistently after multiple injections without affecting bladder compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of therapeutic effect after repeated injections of botulinum toxin type A to treat incontinence due to neurogenic detrusor overactivity. Karsenty, G., Reitz, A., Lindemann, G., et al.[2010]

In a study of 281 women undergoing onabotulinumtoxinA injections for urgency incontinence, using multiple doses of prophylactic antibiotics did not significantly reduce the rate of urinary tract infections compared to a single dose, with infection rates of 13.8% and 10.3% respectively.

The study found that having a positive urine culture within 30 days post-injection greatly increased the odds of developing a urinary tract infection, highlighting the importance of monitoring urine cultures in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary tract infection following intradetrusor onabotulinumtoxina injection for non-neurogenic urgency incontinence: single- vs. multi-dose prophylactic antibiotic treatment regimens. Crouss, T., Kim, Y., Lai, E., et al.[2023]

In a phase III trial involving 248 Japanese patients with overactive bladder, onabotulinumtoxinA significantly reduced daily urinary incontinence episodes by an average of 2.16 compared to placebo, indicating its efficacy in managing this condition.

While onabotulinumtoxinA improved symptoms and patient-reported outcomes, it was associated with a higher incidence of mild to moderate adverse events, such as urinary tract infections and urinary retention, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis). Yokoyama, O., Honda, M., Yamanishi, T., et al.[2022]

Botulinum toxin A (onabotulinumtoxinA) is effective in treating urinary incontinence caused by neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), significantly reducing urinary incontinence and improving quality of life in patients, particularly those with multiple sclerosis and spinal cord injuries.

While the treatment is generally safe, common adverse effects include urinary tract infections and the need for clean intermittent catheterization, especially in NDO patients. Long-term studies confirm the efficacy and safety of onabotulinumtoxinA for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin for genitourinary conditions: What is the evidence? da Silva, CM., Chancellor, MB., Smith, CP., et al.[2018]

OnabotulinumtoxinA (BOTOX) significantly reduces symptoms of overactive bladder, such as urgency and urinary incontinence, compared to placebo, based on a review of eight randomized controlled trials involving 1875 patients.

While effective in alleviating symptoms, onabotulinumtoxinA treatment is associated with a higher incidence of serious side effects, including urinary tract infections and urinary retention, indicating a need for careful consideration of risks versus benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficiency of onabotulinumtoxinA for the treatment of overactive bladder: a systematic review and meta-analysis. Sun, Y., Luo, D., Tang, C., et al.[2022]

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]

OnabotulinumtoxinA injections are a safe and effective second-line treatment for adults with refractory overactive bladder, showing improvement in 60%-65% of patients compared to placebo.

The optimal dose of 100 U, approved by the FDA, provides symptom relief for 6 to 12 months, with a low risk of urinary retention at around 6%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA for the treatment of overactive bladder. Cox, L., Cameron, AP.[2023]

In a study of 284 patients receiving intravesical Botox® for detrusor overactivity, those who took a 3-day course of oral fluoroquinolone antibiotics had a significantly lower rate of urinary tract infections (UTIs) at 20.8% compared to 36% in those who received a single intramuscular dose of ceftriaxone.

The findings suggest that a longer course of antibiotics, especially for patients with a positive preprocedure urine culture, may further reduce the risk of postprocedure UTIs following Botox® injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the ideal antibiotic prophylaxis for intravesically administered Botox injection? A comparison of two different regimens. Houman, J., Moradzadeh, A., Patel, DN., et al.[2020]

Botulinum neurotoxin (BoNT) injections into the bladder wall are an effective alternative for treating neurogenic detrusor overactivity (NDO) and urinary incontinence in patients who cannot tolerate anticholinergic medications, with FDA approval received in 2011.

The treatment has been shown to significantly decrease urinary incontinence and improve quality of life, while also increasing bladder capacity and reducing detrusor pressures, although common side effects include urinary tract infections and urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin in individuals with neurogenic detrusor overactivity: state of the art review. Linsenmeyer, TA.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Is repeat Botulinum Toxin A injection valuable for neurogenic detrusor overactivity-A systematic review and meta-analysis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder-neck dysfunction: objective and patient-reported outcomes. [2018]

4. Australia pubmed.ncbi.nlm.nih.gov

Botulinum toxin treatment for bladder dysfunction. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Persistence of therapeutic effect after repeated injections of botulinum toxin type A to treat incontinence due to neurogenic detrusor overactivity. [2010]

6. England pubmed.ncbi.nlm.nih.gov

Urinary tract infection following intradetrusor onabotulinumtoxina injection for non-neurogenic urgency incontinence: single- vs. multi-dose prophylactic antibiotic treatment regimens. [2023]

7. Australia pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis). [2022]

8. England pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin for genitourinary conditions: What is the evidence? [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The safety and efficiency of onabotulinumtoxinA for the treatment of overactive bladder: a systematic review and meta-analysis. [2022]

10. Korea (South) 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. [2020]

11. England pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA for the treatment of overactive bladder. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Use of Botulinum Toxin in the Genitourinary System. [2021]

13. England pubmed.ncbi.nlm.nih.gov

What is the ideal antibiotic prophylaxis for intravesically administered Botox injection? A comparison of two different regimens. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin in individuals with neurogenic detrusor overactivity: state of the art review. [2022]