Vaginal Estrogen vs Oral Mirabegron for Overactive Bladder

Recruiting in Palo Alto (17 mi)

Overseen by Christopher W Heuer, DO

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Walter Reed National Military Medical Center

Must not be taking: Anticholinergics, Beta-3 agonists

Disqualifiers: Multiple sclerosis, Parkinson's, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a vaginal estrogen cream and an oral pill called Mirabegron in postmenopausal women with overactive bladder symptoms. The cream helps improve bladder function by adding estrogen, while the pill relaxes the bladder to reduce frequent urination.

Will I have to stop taking my current medications?

The trial requires that you have not taken anticholinergic or beta-3 agonists in the past month, so you may need to stop these medications before participating.

What data supports the effectiveness of the drug Mirabegron for overactive bladder?

Research shows that Mirabegron, taken once daily, significantly reduces the number of incontinence and urgency episodes, increases the amount of urine voided, and improves quality of life for people with overactive bladder. It is generally well tolerated and has a lower risk of side effects like dry mouth compared to other treatments. ^{1 2 3 4 5}

Is Mirabegron generally safe for humans?

Mirabegron is generally well tolerated in clinical trials for overactive bladder, with a similar rate of side effects as a placebo over 12 weeks and a low risk of causing heart rhythm issues. ^{2 5 6 7 8}

How does the drug Mirabegron differ from other treatments for overactive bladder?

Mirabegron is unique because it is a β3-adrenergic receptor agonist, which helps relax the bladder muscle to increase its storage capacity, unlike other treatments that may work by reducing bladder contractions. It is taken orally once daily and has been shown to improve symptoms of overactive bladder with a favorable side effect profile, including a lower risk of dry mouth compared to some other medications. ^{1 2 3 5 9}

Research Team

Christopher W Heuer, DO

Principal Investigator

Urogynecology Fellow

Eligibility Criteria

This trial is for postmenopausal women with overactive bladder symptoms who can read and speak English. They must have had no periods for 12 months, or certain surgeries, or high hormone levels. Women with significant pelvic issues, neurological conditions like MS or Parkinson's, a history of pelvic radiation, interstitial cystitis, frequent UTIs, or recent use of similar meds cannot join.

Inclusion Criteria

Ability to speak and read English

Your score on the OAB-q SF questionnaire is 14 or higher (which is adjusted to 20).

You are a woman who has stopped having periods for at least a year, had both ovaries removed at least a year ago, had a hysterectomy and still have ovaries and are over 55 years old, or have a specific hormone level.

Exclusion Criteria

You have severe pelvic organ prolapse and cannot use vaginal estrogen therapy.

You have a medical reason that prevents you from using vaginal estrogen or mirabegron.

You have had unexplained vaginal bleeding after menopause in the last year.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomized to receive either vaginal estradiol or oral Mirabegron for 12 weeks

12 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, completing questionnaires and diaries

4 weeks

1 visit (in-person)

Extension

Participants may opt into dual treatment with both vaginal estradiol and Mirabegron for an additional 12 weeks

12 weeks

Treatment Details

Interventions

• Mirabegron 50 MG [Myrbetriq] (Beta-3 Agonist)
• Vaginal estrogen (Hormone Therapy)

Trial Overview The study compares vaginal estradiol cream against an oral beta-3 agonist called Mirabegron for treating overactive bladder in postmenopausal women. Participants will be randomly assigned to receive either the estradiol cream with a placebo pill or Mirabegron pills with a placebo cream for 12 weeks.

Participant Groups

Group I: Vaginal Estradiol with placebo oral pill Active Control 1 Intervention

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

Group II: Oral Mirabegron with placebo vaginal cream Active Control 1 Intervention

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

Mirabegron 50 MG [Myrbetriq] is already approved in Canada, Japan for the following indications:

Approved in Canada as Myrbetriq for:

• Overactive bladder syndrome (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in Japan as Betmiga for:

• Overactive bladder syndrome (OAB)
• Neurogenic detrusor overactivity (NDO)

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Melissa C. Austin

Walter Reed National Military Medical Center

Chief Executive Officer since 2020

MD from University of Colorado Health Sciences Center

Melissa C. Austin

Walter Reed National Military Medical Center

Chief Medical Officer since 2020

MD, Board Certified in Anatomic and Clinical Pathology

Findings from Research

In a study of 60 treatment-naïve women with overactive bladder, mirabegron (50 mg daily for 12 weeks) significantly reduced subjective symptoms, as indicated by a decrease in the OAB symptom score from 9.4 to 6.2 points.

Mirabegron improved storage function parameters, such as the first desire to void and maximum cystometric capacity, and led to the disappearance of detrusor overactivity in 40% of patients, while not affecting voiding function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urodynamic evaluation of the efficacy of mirabegron on storage and voiding functions in women with overactive bladder. Matsukawa, Y., Takai, S., Funahashi, Y., et al.[2015]

In a study of 85 sexually active women with overactive bladder, those treated with mirabegron for 3 months showed significant improvements in sexual function across all measured domains, including desire, arousal, lubrication, orgasm, satisfaction, and pain.

In contrast, the control group that did not receive treatment showed no significant changes in sexual function, highlighting mirabegron's potential benefits for women experiencing both overactive bladder and sexual dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mirabegron, used for overactive bladder treatment, on female sexual function: a prospective controlled study. Zachariou, A., Mamoulakis, C., Filiponi, M., et al.[2018]

Mirabegron, a β3-adrenoceptor agonist, has been shown to effectively reduce micturition frequency and improve quality of life in patients with overactive bladder (OAB) over a 12-week treatment period, with benefits sustained for up to 52 weeks.

Compared to traditional antimuscarinics, mirabegron is generally well tolerated, with a lower incidence of dry mouth, making it a suitable alternative for patients who cannot tolerate antimuscarinics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: A Review in Overactive Bladder Syndrome. Deeks, ED.[2018]

Mirabegron, a β3-adrenergic receptor agonist, significantly reduces incontinence and micturition episodes in adults with overactive bladder syndrome, based on three 12-week trials involving multiple countries.

It is generally well tolerated, with a low adverse event rate similar to placebo, and has a lower incidence of dry mouth compared to tolterodine, making it a favorable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: a review of its use in patients with overactive bladder syndrome. Sanford, M.[2021]

In a 12-week study involving Japanese female patients with overactive bladder, both mirabegron and vibegron were found to be effective, showing no significant differences in their ability to improve symptoms based on the total overactive bladder symptom scores (OABSS).

However, mirabegron demonstrated a better safety profile, with significantly fewer treatment-related adverse events (19.1% for mirabegron vs. 38.5% for vibegron), suggesting that mirabegron may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron versus vibegron in previously untreated female patients with overactive bladder: A randomized, single-clinic, open-label trial. Sato, H., Otsuka, S., Tsukada, S.[2023]

Mirabegron, a beta-3 adrenergic agonist, has been approved for treating neurogenic detrusor overactivity in pediatric patients aged 3 years and older, marking a significant advancement in pediatric urology.

The medication is available in two formulations: extended-release tablets for children weighing 35 kg or more, and an extended-release oral suspension for those under 35 kg, emphasizing the importance of appropriate dosing based on weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. Keam, SJ.[2021]

References

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

Urodynamic evaluation of the efficacy of mirabegron on storage and voiding functions in women with overactive bladder. [2015]

2. England pubmed.ncbi.nlm.nih.gov

The impact of Mirabegron on sexual function in women with idiopathic overactive bladder. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The effect of mirabegron, used for overactive bladder treatment, on female sexual function: a prospective controlled study. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Mirabegron: A Review in Overactive Bladder Syndrome. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Mirabegron: a review of its use in patients with overactive bladder syndrome. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Mirabegron versus vibegron in previously untreated female patients with overactive bladder: A randomized, single-clinic, open-label trial. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. [2021]

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

Comparison of Mirabegron and Vibegron in Women With Treatment-Naive Overactive Bladder: A Randomized Controlled Study. [2023]

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

Comparisons of the Clinical Outcomes and Urodynamic Effects of Mirabegron versus Tolterodine Treatment for Female Overactive Bladder Syndrome: A Subgroup Analysis of a Controlled, Randomised, Prospective Study. [2018]