Clinical trial NCT05221021: Vaginal Estradiol vs Oral Beta-3 Agonist for Overactive Bladder Syndrome
Official title: Vaginal Estradiol vs Oral Beta-3 Agonist for Treatment of Overactive Bladder Syndrome: A Single-Therapy, Double-Blind, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Overactive Bladder Syndrome
Lead sponsor: Walter Reed National Military Medical Center
Sponsor class: FED
First posted: 2022-02-02
Enrollment: 152
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single site, double blinded, randomized controlled trial of Mirabegron vs Vaginal Estradiol for overactive bladder syndrome
Primary purpose: TREATMENT

Brief summary: A single site, double-blinded, randomized controlled trial for postmenopausal women with urinary frequency, urgency, nocturia with or without urgency urinary incontinence symptoms. Patient's will be randomized between 0.01% vaginal estradiol cream with placebo oral pill or daily 50 milligrams oral Mirabegron with a placebo vaginal cream for 12 weeks.

Detailed description: Background/significance: Overactive Bladder Syndrome (OAB) is defined as urinary urgency, with or without urgency incontinence, and usually accompanied by frequency and nocturia. OAB remains an increasingly more prevalent disease, affecting over 45% of postmenopausal women over the age 65 within the United States. Epidemiological research continues to consistently highlight OAB's impact on patience's mental health, sleep quality, physical activity, occupational productivity and overall quality of life. OAB's economic burden cannot be overstated as well as a US cost-of-illness study reported a total cost of $66 billion in 2007 and estimated cost of over $82 billion in 2021.

Mainstay first-line forms of management for OAB include behavioral modifications such as bladder training (timed voiding, urge suppression techniques), pelvic floor physical therapy, fluid management and bladder irritant restrictions. Second-line forms of management consistent of pharmacotherapy including oral anticholinergics or beta-3 adrenoreceptor agonists. Multiple studies have shown that vaginal estrogen improves symptoms of urinary urgency and frequency in postmenopausal women. Limited data currently exist comparing beta-3 antagonists to vaginal estrogen use for overactive bladder syndrome as well as the combination of both.

Purpose: This study aims to compare the efficacy of vaginal estradiol with that of oral mirabegron in the treatment of overactive bladder in postmenopausal women and characterize outcomes in women undergoing combined therapy.

Study design: This is a single site, double-blinded, randomized controlled trial for 152 postmenopausal women with urinary frequency, urgency, nocturia with or without urgency urinary incontinence symptoms. Patient's will be randomized between 0.01% vaginal estradiol cream 1/2 gram once nightly for two weeks then three times per week or 50 milligrams oral Mirabegron once a night.

Procedures: Postmenopausal women with bothersome OAB symptoms will be eligible for the study. OAB symptoms will be based on the OAB-q (SF) symptom bother questionnaire with an initial score greater than 20. Other inclusion criteria include ability to speak English. Exclusion criteria include: Post void residual \>200mL or \>1/3 patient's total bladder volume, currently on or previously taking anticholinergic or beta- 3 antagonists within the past 1 month, untreated, symptomatic pelvic organ prolapse greater than Stage 2, contraindication to vaginal estrogen therapy, contraindication to Mirabegron, undiagnosed postmenopausal vaginal bleeding within the past 12 months, current diagnosis of a condition which explains their overactive bladder or incontinence symptoms.

Participants who elect to enroll will have a post-void residual determined, a demographic sheet, the OAB-q (SF) health-related quality of life (HRQL) questionnaire, a 24-hour voiding diary and Patient Global Impression of Severity (PGI-S). Participants will be randomized via random allocation rule fixed blocking in a 1:1 ratio to either vaginal estrogen or oral Mirabegron. After 12 weeks of single therapy, the patients will be contacted for follow up to complete all previous questionnaires, a 24-hour voiding diary as well as the PGI-I questionnaire. After the initial 12-weeks, single therapy follow up appointment, participants will be offered dual treatment (both vaginal estrogen and Mirabegron same doses/frequencies.) If the patient agrees she will receive dual treatment for 12 weeks and follow up with the same questionnaires.

Eligibility criteria: Inclusion Criteria:

* Raw score of 14 or more on OAB-q SF (adjusted score of 20)
* Postmenopausal defined by not having a period for 12 months or bilateral oophorectomy a least 12 months status post procedure, or women with prior hysterectomy and preserved ovaries over age 55 years old or having a documented follicle stimulating hormone level greater than 40mIU/mL.
* Ability to speak and read English

Exclusion Criteria:

* Contraindications to Vaginal Estrogen or Mirabegron
* Post void residual \>200mL or \>1/3 patient's total bladder volume
* Currently on or previously taking anticholinergic or beta- 3 agonists within the past 1 month
* Symptomatic pelvic organ prolapse greater than Stage 2, contraindication to vaginal estrogen therapy
* Undiagnosed postmenopausal vaginal bleeding within the past 12 months
* Current diagnosis of Multiple sclerosis, Parkinson's Disease, prior spinal cord injury, Spina Bifida, prior pelvic irradiation, Interstitial Cystitis, recurrent urinary tract infection.

Primary outcomes:
measure: OAB-q short form (SF) symptom bother scores
timeFrame: 12 weeks
Secondary outcomes:
measure: health-related quality of life (HRQL) of the OAB-q SF scores
timeFrame: 12 weeks
measure: Patient Global Impression of Severity (PGI-S) scores
timeFrame: 12 weeks
measure: Patient Global Impression of Improvement (PGI-I) scores
timeFrame: 12 weeks
measure: Number of voids
timeFrame: 12 weeks
measure: Number of urge incontinence episodes
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
Study officials:
affiliation: Urogynecology Fellow
name: Christopher W Heuer, DO
role: PRINCIPAL_INVESTIGATOR
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