Clinical trial NCT05512039: Reduced-dose Botox for Urgency Incontinence Among Elder Females
Official title: Reduced-dose onabotuLinumtoxinA for Urgency Incontinence Among Elder Females (RELIEF): A Randomized Controlled Comparative Effectiveness Trial With Embedded Qualitative and Costing Analyses
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Overactive Bladder
Urinary Incontinence in Old Age
Urgency Urinary Incontinence
Keywords: Urinary Incontinence
Urgency Urinary Incontinence
Overactive Bladder
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Dartmouth College
name: University of Alabama at Birmingham
name: University of Pittsburgh
name: University of Texas
name: Kaiser Permanente
name: Oregon Health and Science University
name: Stanford University
name: University of Connecticut
name: University of Nebraska
First posted: 2022-08-23
Enrollment: 376
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The purpose of this quadruple-masked, randomized-controlled study is to study the treatment of urgency urinary incontinence (UUI) specifically among older women with low- versus standard-dose of onabotulinumtoxinA (BTX) via: symptom-specific and health-related quality of life (QOL; Aim 1), patient-reported and clinical outcome measures including adverse events (Aim 2), qualitative experience with focused interviews (Aim 3) and cost burden and economic impact (Aim 4). This study is an active collaboration between researchers in Gynecology, Urology, and Geriatrics at Dartmouth Hitchcock Medical Center (DHMC) and at 6 other centers; University of Alabama (UAB), University of Pittsburgh (U Pitt), University of Texas Southwestern (UTSW), Kaiser Permanente of Southern California (KPSCP), Oregon Health \& Sciences University (OHSU), and University of Nebraska Medical Center (UNMC; joined January 2025). The investigators also have collaborators at Stanford University and University of Connecticut, though those sites are not recruiting participants.

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.

Primary outcomes:
measure: Change in symptom specific quality of life and bother over time.
timeFrame: Baseline, monthly post-injection through 12 months post-injection; primary outcome is at 3 months post-injection.
Secondary outcomes:
measure: Symptom severity
timeFrame: Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.
measure: Symptom bother
timeFrame: Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.
measure: Change in number of urgency urinary incontinence (UUI) episodes per day.
timeFrame: Baseline, and 1, 3, and 6 months post injection
measure: Change in Global Symptom Improvement
timeFrame: Baseline,3, 6, & 12 months post injection
measure: Goal setting and attainment
timeFrame: Baseline & 3 months post injection.
measure: Change in general health-related quality of life as measure by the Health Utility Index-3
timeFrame: Baseline, 3 6 and 12 months
measure: Depression
timeFrame: Baseline, 3, 6 and 12 months post injection. Results will be compared at the end of the 3 month post injection.
measure: Procedural discomfort and adverse events
timeFrame: Day of injection and monthly through 12 months
measure: Qualitative experience of BTX treatment and adverse events
timeFrame: Baseline & 3 months post injection
measure: Survey of economic burden
timeFrame: Baseline, 3 & 12 months. Results will be compared at the end of the 12 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: San Diego
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Anne C Cooper, MD, MA
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: E A Gormley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amundsen CL, Komesu YM, Chermansky C, Gregory WT, Myers DL, Honeycutt EF, Vasavada SP, Nguyen JN, Wilson TS, Harvie HS, Wallace D; Pelvic Floor Disorders Network. Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial. Eur Urol. 2018 Jul;74(1):66-73. doi: 10.1016/j.eururo.2018.02.011. Epub 2018 Feb 24.
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citation: Monz B, Pons ME, Hampel C, Hunskaar S, Quail D, Samsioe G, Sykes D, Wagg A, Papanicolaou S. Patient-reported impact of urinary incontinence--results from treatment seeking women in 14 European countries. Maturitas. 2005 Nov 30;52 Suppl 2:S24-34. doi: 10.1016/j.maturitas.2005.09.005. Epub 2005 Nov 16.
citation: Furlong WJ, Feeny DH, Torrance GW, Barr RD. The Health Utilities Index (HUI) system for assessing health-related quality of life in clinical studies. Ann Med. 2001 Jul;33(5):375-84. doi: 10.3109/07853890109002092.
citation: Horsman J, Furlong W, Feeny D, Torrance G. The Health Utilities Index (HUI): concepts, measurement properties and applications. Health Qual Life Outcomes. 2003 Oct 16;1:54. doi: 10.1186/1477-7525-1-54.
citation: Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol. 2003 Jul;189(1):98-101. doi: 10.1067/mob.2003.379.