Reduced-dose Botox for treating urgency incontinence in older women

Reduced-dose onabotuLinumtoxinA for Urgency Incontinence Among Elder Females (RELIEF): A Randomized Controlled Comparative Effectiveness Trial With Embedded Qualitative and Costing Analyses

This study is testing whether lower doses of Botox can help older women with urgency urinary incontinence feel better compared to the standard dose.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 376 (estimated)
• Ages: 70 Years and up
• Sex: Female
• Sponsor: Dartmouth-Hitchcock Medical Center (Academic / other)
• Locations: 7 sites (Birmingham, Alabama and 6 other locations)
• Trial ID: NCT05512039 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of reduced versus standard doses of onabotulinumtoxinA (Botox) injections for treating urgency urinary incontinence (UUI) in women aged 70 and older. It employs a quadruple-masked, randomized-controlled design to assess symptom-specific outcomes, health-related quality of life, patient-reported outcomes, and economic impact. The study involves collaboration among multiple institutions, including Dartmouth Hitchcock Medical Center and several universities, to gather comprehensive data on treatment efficacy and patient experiences.

Who should consider this trial

Good fit: Ideal candidates for this study are women aged 70 and older who experience refractory urgency urinary incontinence.

Not a fit: Patients who do not have urgency urinary incontinence or those who have not tried conservative treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective and potentially safer treatment option for older women suffering from urgency urinary incontinence.

How similar studies have performed: Other studies have shown promise in using Botox for urinary incontinence, but this specific approach of reduced dosing is novel.

Eligibility criteria

Inclusion Criteria:

1. Adult female at least 70 years old at date of enrollment
2. Urgency urinary incontinence (urge incontinence \> stress incontinence per screening criteria)
3. On average 2 or more urgency or insensible incontinence episodes per day per patient report
4. Refractory urinary urgency incontinence, defined as

   1. Persistent symptoms despite trial of one or more conservative treatments (e.g. behavioral therapy, physical therapy, home Kegel exercises); participants not required to have attempted first line therapies if deemed not feasible or appropriate by provider with input of participant/caregiver.
   2. Persistent symptoms despite the use of anticholinergic and/or beta-3 agonist medication; or inability to tolerate medication due to side effects, or has a contraindication to taking medication, or is unable to afford the cost of the medication.
5. Currently not on an anticholinergic or beta-3 agonist medication or is willing to stop medication for 3 weeks prior to completing baseline bladder tally, with plan to remain off medication through duration of the study. Currently not actively using sacral neuromodulation therapy (either has not tried, or unit has been off for 4 weeks prior to baseline bladder tally and will remain turned off for the duration of the study). It is permissible for participants to continue self-led conservative therapies during participation in the study, including Kegel exercises, avoidance of bladder irritants, and urge suppression.
6. Willing and able to complete all study-related items, with assistance of caregiver(s) if needed.
7. Demonstrates awareness of possible need for catheterization in event of post-injection urinary retention \& acknowledges risks of catheterization. Participant does not need to demonstrate ability to perform self-catheterization.
8. Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function. Patients with a diagnosis of Parkinson's disease or diabetes may be eligible provided they have a grossly normal neurologic exam and otherwise fulfill the inclusion/exclusion criteria.

Exclusion Criteria:

1. Lack of capacity to provide consent. Will be assessed if needed per judgment of the site PI and study staff, with use of optional questionnaire.
2. Baseline persistently elevated post-void residual \[PVR\] (\>150mL on 2 occasions in the 6 weeks prior to enrollment). If the PVR was obtained via bladder scanner with measurements differing by more than 100mL, or if there is concern about the accuracy of the scanner, it will be confirmed via catheterization which will be considered the gold standard.
3. Need for BTX injection to take place in the Operating Room or under sedation. (Of note, for repeat injection under the protocol, patients may have OR injection if indicated due to pain with initial BTX injection.)
4. Previous treatment with intravesical BTX in the last 12 months or use of sacral neuromodulation therapy within the past 4 weeks (unit may remain implanted, but should remain off for duration of the study).
5. Untreated symptomatic urinary tract infection (UTI). Eligible once UTI treatment complete and symptoms resolved.
6. Known bladder abnormality, including current or prior bladder malignancy, carcinoma in situ or untreatable cystitis (e.g. eosinophilic cystitis); prior major bladder surgery that would alter the detrusor muscle, such as augmentation cystoplasty; or hematuria that has not been evaluated.
7. Neurogenic detrusor overactivity or neurologic disease that may impact bladder function, including stroke, multiple sclerosis, peripheral neuropathy, spinal cord injury. Conditions such as Parkinson's disease and diabetes are acceptable provided normal bladder emptying and grossly normal neurologic function.
8. Concurrent BTX use for other indication, participants cannot exceed 300 units BTX in a 3 month period. Participants who may have conflict between study BTX administration and administration for other purposes may be excluded from participation if there is concern that study drug administration will be compromised. Concurrent use of BTX for another indication that would not exceed 300 units in a 3 month period, or that can have time of administration of the other BTX adjusted to avoid excessive dose, is acceptable; for instance, for migraines.
9. Greater than stage 2 pelvic floor prolapse, uncorrected or persistent despite pessary use (leading edge of prolapse not greater than 1cm beyond the hymen). Ongoing pessary use is permissible. Patients may have had a prior repair for pelvic organ prolapse. (see chart review of recent exam or perform brief exam while collecting post-void residual)
10. Planned prolapse or stress incontinence surgery; would defer enrollment to \>3 months post-operative.
11. Allergy or intolerance to lidocaine or BTX.
12. Participation in another research study that could conflict with the RELIEF study, in estimation of the site PI.

Where this trial is running

Birmingham, Alabama and 6 other locations

• University of Alabama - Birmingham — Birmingham, Alabama, United States (Recruiting)
• Kaiser Permanente Medical Group — San Diego, California, United States (Recruiting)
• University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)
• Dartmouth-Hitchcock Medical Center — Lebanon, New Hampshire, United States (Recruiting)
• Oregon Health & Science University — Portland, Oregon, United States (Recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Anne C Cooper, MD, MA — Dartmouth-Hitchcock Medical Center
• Study coordinator: Deborah J Johnson, MHA

Conditions Overactive Bladder; Urinary Incontinence in Old Age; Urgency Urinary Incontinence; Urinary Incontinence