Low-Dose Botox for Urinary Incontinence

(RELIEF Trial)

Recruiting at 6 trial locations

Overseen By Jasmine Tan-Kim, MD

Age: 65+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Dartmouth-Hitchcock Medical Center

Must not be taking: Anticholinergics, Beta-3 agonists

Disqualifiers: Neurologic disease, Bladder abnormality, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day

376 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of Botox to treat urgency urinary incontinence (UUI) in women aged 70 and older. Researchers aim to determine if a lower dose of Botox is as effective as the standard dose when injected into the bladder. Women over 70 who experience frequent sudden urges to urinate despite other treatments may be eligible for this study. Participants should be willing to stop certain medications and discuss the trial with their healthcare provider. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

Yes, if you are currently taking anticholinergic or beta-3 agonist medications, you will need to stop them for 3 weeks before starting the trial and remain off them during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Botox, also known as onabotulinumtoxinA, is generally safe for treating conditions like urinary incontinence. Studies have found it effective, though some people might experience side effects. For instance, one study found that about 1 in 4 women who received repeated Botox injections for bladder issues developed urinary tract infections (UTIs). Another study noted possible issues like increased urine retention and sudden difficulty urinating.

Despite these potential side effects, many choose Botox because it is considered safer than other treatments. Most people tolerate it well, without severe reactions. Since the FDA has approved Botox for other uses, like treating overactive bladder (OAB), additional evidence suggests it is generally safe.

This study compares a standard dose to a lower dose, which might further reduce risks. These findings can help reassure prospective participants about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for urinary incontinence, such as pelvic floor exercises, medications like anticholinergics, or surgical options, the investigational low-dose Botox treatment offers a new approach. While traditional Botox treatments use a standard dose of 100 units, this study explores the efficacy of a lower dose of 50 units injected directly into the bladder. Researchers are excited because this lower dose could potentially offer fewer side effects while still effectively reducing symptoms, making it a promising alternative for patients seeking less invasive solutions.

What evidence suggests that this trial's treatments could be effective for urinary incontinence?

Research has shown that Botox, also known as onabotulinumtoxinA, can significantly aid individuals with urgency urinary incontinence (UUI), a condition characterized by a sudden need to urinate. In this trial, participants will receive either a standard dose or a low dose of Botox. One study found that more than half of the patients who received a low dose stopped experiencing incontinence and were completely dry just six weeks after treatment. Patients also reported improved quality of life following this treatment. Another study found that both regular and lower doses effectively treated UUI, indicating that even a smaller dose can provide significant relief for those dealing with this condition. ^{1 2 6 7 8}

Who Is on the Research Team?

E A Gormley, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Anne C Cooper, MD, MA

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

This trial is for women aged 70 or older with urgency urinary incontinence who've tried other treatments without success. They should be able to handle catheterization if needed, have no major neurological issues affecting bladder function, and not be using certain medications or therapies that could interfere with the study.

Inclusion Criteria

Demonstrates awareness of possible need for catheterization in event of post-injection urinary retention & acknowledges risks of catheterization

I am a woman aged 70 or older.

I experience 2 or more sudden urges to urinate or involuntary urine leaks daily.

Exclusion Criteria

I plan to have surgery for prolapse or incontinence but can join the trial 3 months after.

You are allergic or can't tolerate lidocaine or BTX.

Participation in another research study that could conflict with the RELIEF study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a standard dose (100 units) or a low dose (50 units) of onabotulinumtoxinA injected into the bladder

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of symptom severity, quality of life, and adverse events

12 months

Monthly visits (in-person or virtual)

Qualitative Interviews

Participants undergo focused interviews to assess qualitative experience with BTX treatment

3 months

2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Botox

Trial Overview

The study compares two doses of Botox injections (50 units vs. 100 units) in treating urinary urgency among elderly females. It aims to determine whether a reduced dose can effectively manage symptoms while potentially minimizing side effects.

How Is the Trial Designed?

Group I: Botox: Low dose Experimental Treatment 1 Intervention

A lower dose of 50 units of botox will be injected into the bladder.

Group II: Botox: Standard dose Active Control 1 Intervention

The standard dose of 100 units of botox will be injected into the bladder.

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

Approved in United States as Botox for:

• Overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
• Urinary incontinence due to detrusor overactivity associated with a neurologic condition

Approved in European Union as Botox for:

• Overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Dartmouth College

Collaborator

Trials

93

Recruited

1,415,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Kaiser Permanente

Collaborator

Trials

563

Recruited

27,400,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

University of Connecticut

Collaborator

Trials

194

Recruited

162,000+

Published Research Related to This Trial

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]

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]

Botulinum toxin-A (BTX-A), specifically OnabotulinumtoxinA, has been shown to significantly improve urinary incontinence and quality of life in patients with neurogenic detrusor overactivity and idiopathic overactive bladder, based on large randomized placebo-controlled trials.

Lower doses of OnabotulinumtoxinA (100 U) are effective for treating overactive bladder with an acceptable safety profile, while results for benign prostatic hyperplasia are mixed, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin-what urologic uses does the data support? Seth, J., Khan, MS., Dasgupta, P., et al.[2021]

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]

In a study of 313 patients with idiopathic overactive bladder (OAB), onabotulinumtoxinA (BOTOX®) significantly reduced urinary urgency incontinence (UUI) episodes and improved urodynamic parameters, particularly at doses of 100 U or higher, compared to placebo.

The treatment was effective regardless of whether patients had detrusor overactivity (DO) at baseline, indicating that the success of onabotulinumtoxinA in managing OAB is not dependent on the presence of DO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder. Rovner, E., Kennelly, M., Schulte-Baukloh, H., et al.[2022]

Onabotulinum toxin A is effective for treating urinary incontinence due to neurogenic detrusor overactivity and idiopathic detrusor overactivity, with significant improvements in urinary symptoms, quality of life, and bladder capacity after injections of 200 U and 100 U, respectively.

Adverse events from treatment are generally mild, primarily involving urinary tract infections and urinary retention in a small percentage of patients, and the effects of the treatment are temporary, requiring repeated injections for sustained benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin treatment for bladder dysfunction. Santos-Silva, A., da Silva, CM., Cruz, F.[2013]

Botulinum toxin injections, specifically OnabotulinumtoxinA, are recognized as a safe and effective treatment for refractory urinary incontinence, particularly in patients who do not respond to or cannot tolerate anticholinergic medications.

There are two approved uses for OnabotulinumtoxinA: 200 U for urinary incontinence due to neurological conditions and 100 U for overactive bladder symptoms, highlighting its versatility in treating different types of urinary incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Botulinum Toxin in the Genitourinary System. Chancellor, MB., Smith, CP.[2021]

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 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]

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]

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This study evaluates the efficacy of intravesical botulinum toxin for UUI and identifies factors influencing treatment outcomes.

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Safety and Efficacy Study of OnabotulinumtoxinA for the ...

This study will evaluate the safety and efficacy of OnabotulinumtoxinA (BOTOX®) for the treatment of urinary incontinence due to NDO in non-catheterizing ...

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