Vaginal Estradiol vs Oral Beta-3 Agonist for Overactive Bladder Syndrome

August 15, 2024 updated by: Christopher W. Heuer, DO, Walter Reed National Military Medical Center

Vaginal Estradiol vs Oral Beta-3 Agonist for Treatment of Overactive Bladder Syndrome: A Single-Therapy, Double-Blind, Randomized Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

152

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20889
        • Recruiting
        • Walter Reed National Military Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vaginal Estradiol with placebo oral pill
Patient will receive 0.01% estradiol cream 1/2 gram applied vaginally once nightly for two weeks then three times per week with once daily placebo oral pill
Drug: Vaginal estrogen
0.01% estradiol cream 1/2 gram applied vaginally once nightly for two weeks then three times per week with once daily placebo oral pill
Other Names:
  • Estrace
  • Estradiol
  • Micronized Estrogen
Active Comparator: Oral Mirabegron with placebo vaginal cream
Patient will receive 50 milligrams oral Mirabegron once daily and placebo vaginal cream (Medisca's VersaPro Cream Base) once nightly for two weeks then three times per week
Drug: Mirabegron 50 MG [Myrbetriq]
50mg oral Mirabegron once daily
Other Names:
  • Myrbetriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OAB-q short form (SF) symptom bother scores
Time Frame: 12 weeks

Primary Aim: Compare changes in the six-item OAB-q short form (SF) symptom bother scores from baseline to 12 weeks post treatment in postmenopausal women who receive either vaginal estradiol or Mirabegron. We will also compare 12-weeks post treatment OAB-q SF symptom bother scores after single therapy trials with patients who desire combined therapy for another 12 weeks.

The OAB-q SF symptom bother questionnaire is based on six individual questions a 6-point scale ranging from 1 or "not at all" to 6 or "a very great deal." Per the guidance of the scoring manual, the raw scores are converted into scores ranging from 0 to 100 (0 being the minimum score and 100 being the maximum score.) The higher the score signifies that the patient has worse bothersome overactive bladder symptoms. The conversion to a 100 point scale is based on the equation as follows: ((Raw score - 6) / 36) x 100.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
health-related quality of life (HRQL) of the OAB-q SF scores
Time Frame: 12 weeks

Compare health-related quality of life (HRQL) of the OAB-q SF from baseline to 12 weeks post treatment. We will also compare 12-weeks post treatment HRQL scores after single therapy trials with patients who desire combined therapy for another 12 weeks.

The health-related quality of life (HRQL) portion of the OAB-q SF is based on 13 individual questions a 6-point scale ranging from 1 or "none of the time" to 6 or "all of the time" with the lowest score being 13 to the highest score being 78. The higher the score signifies that the patient has worse overactive bladder symptoms that affect their quality of life.
12 weeks
Patient Global Impression of Severity (PGI-S) scores
Time Frame: 12 weeks

Compare Patient Global Impression Severity (PGI-S) scores at baseline versus 12 weeks post treatment. We will also compare 12-weeks post treatment Patient Global Impression of Severity (PGI-S) scores after single therapy trials with patients who desire combined therapy for another 12 weeks.

The Patient Global Impression Severity (PGI-S) is a single question which describes the severity of their urinary tract condition. It is a single question on a scale ranging from 1 "not present" to 7 "extremely severe." The higher the score signifies that the patient has worse severity of their symptoms.
12 weeks
Patient Global Impression of Improvement (PGI-I) scores
Time Frame: 12 weeks

Evaluate Patient Global Impression of Improvement (PGI-I) scores at 12 weeks post treatment. We will also compare 12-weeks post treatment Patient Global Symptom Improvement (PGI-I) scores after single therapy trials with patients who desire combined therapy for another 12 weeks.

The Patient Global Impression of Improvement (PGI-I) is a single question which describes how their urinary tract condition is compared to how it was before treatment. It is a single question on a scale ranging from 1 "very much improved" to 7 "very much worse." The higher the score signifies that the patient has worse symptoms compared to prior treatment, the lower the score signifies that the patient has improved symptoms compared how it was before treatment. A score of 4 signifies not change in their described symptoms compared with how it was before treatment.
12 weeks
Number of voids
Time Frame: 12 weeks
Compare number of times the patient voids via 24-hour bladder diary at baseline and 12 weeks post treatment. We will also compare 12-weeks post treatment number of voids after single therapy trials with patients who desire combined therapy for another 12 weeks. This is an objective measurement of how many times the patient voids over a 24 hour time frame post treatment. Though unlikely the lowest quantity would be 0 throughout the day. The more the patient documents voiding throughout the day the signifies worse the patient's described overactive bladder symptoms.
12 weeks
Number of urge incontinence episodes
Time Frame: 12 weeks
Compare number of urge incontinence episodes via 24-hour bladder diary at baseline and 12 weeks post treatment. We will also compare 12-weeks post treatment number of urge incontinence episodes after single therapy trials with patients who desire combined therapy for another 12 weeks. This is an objective measurement of how many times the patient has urge incontinence episodes over a 24 hour time frame post treatment. Though unlikely the lowest quantity would be 0 throughout the day. The more the patient documents voiding throughout the day the signifies worse the patient's described overactive bladder symptoms.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Walter Reed National Military Medical Center

Investigators

  • Principal Investigator: Christopher W Heuer, DO, Urogynecology Fellow

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2022

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

January 30, 2027

Study Registration Dates

First Submitted

December 22, 2021

First Submitted That Met QC Criteria

January 31, 2022

First Posted (Actual)

February 2, 2022

Study Record Updates

Last Update Posted (Actual)

August 19, 2024

Last Update Submitted That Met QC Criteria

August 15, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21-14282

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe