Low-Dose Botox for Urinary Incontinence

(RELIEF Trial)

Recruiting at 6 trial locations

Overseen By Gary Lemack, 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to study the treatment of urgency urinary incontinence (UUI), specifically among women 70 years and older, by comparing reduced versus standard dose of onabotulinumtoxinA (BTX; trade name BOTOX(c)) injection in the bladder.

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.

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

Research shows that Botox (OnabotulinumtoxinA) is effective in reducing urinary incontinence and improving quality of life in patients with conditions like neurogenic detrusor overactivity and overactive bladder. It has been shown to decrease the frequency of incontinence episodes and improve bladder function in these patients. ^{1 2 3 4 5}

Is low-dose Botox safe for treating urinary incontinence?

Botox (onabotulinumtoxinA) is generally safe for treating urinary incontinence, but some people may experience side effects like urinary tract infections and temporary difficulty urinating. Studies show that these side effects are usually mild and manageable, and the treatment has been used safely in various conditions. ^{4 5 6 7 8}

How does the drug Botox differ from other treatments for urinary incontinence?

Botox (OnabotulinumtoxinA) is unique because it is injected directly into the bladder muscle to reduce urinary incontinence, especially for those who haven't responded to other treatments like behavioral therapy or oral medications. It works by relaxing the bladder muscle, providing symptom relief for 6 to 12 months, and can be repeated safely. ^{3 4 7 9 10}

Research Team

Anne C Cooper, MD, MA

Principal Investigator

Dartmouth-Hitchcock Medical Center

E A Gormley, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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 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]

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]

References

1. 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]

2. United States 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. [2022]

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

Botulinum toxin-what urologic uses does the data support? [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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. England pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA for the treatment of overactive bladder. [2023]

8. United States 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. [2018]

9. Australia pubmed.ncbi.nlm.nih.gov

Botulinum toxin treatment for bladder dysfunction. [2013]

10. Germany pubmed.ncbi.nlm.nih.gov

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