Physical Therapy vs Medication for Overactive Bladder in Older Women

Overseen By Steve Fisher, PT, PhD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Antimuscarinics, Digoxin

Disqualifiers: Psychiatric conditions, Genitourinary cancer, Neurologic conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 18

Duration: 12 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to conduct a randomized pilot multi-arm clinical trial comparing a standard course of physical therapist provided pelvic floor muscle training (PFMT) to pharmacologic therapy for the treatment of urgency urinary incontinence (UUI) or Overactive Bladder (OAB) in older women at high risk of falling. The central hypotheses for this project are i) a randomized pilot multi-arm clinical trial comparing PFMT to drug treatment for UUI or OAB in older women at high risk of falling is feasible; and ii) treatment approach can influence both UI and fall related outcomes in this patient population. The main questions it aims to answer are: 1) Is a multi-arm clinical trial comparing PFMT to drug treatment for UUI or OAB in older women at high risk of falling feasible? and 2) How does treatment approach influence both OAB and fall related outcomes in this patient population? Women (16 per arm) 60 years and older with UUI or OAB who screen positive for high fall risk will be randomized to one of three standard of care treatment arms and followed for six months. The three treatment arms are i) a 12-week structured behaviorally based pelvic floor muscle training (PFMT) intervention administered by physical therapists in the clinic; ii) a 12-week course of the beta-3 agonist, Mirabegron; and iii) a 12-week course of the antimuscarinic, Trospium Chloride. Researchers will compare study feasibility and OAB symptom related outcomes across the three groups to see if a larger clinical trial is warranted.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking other antimuscarinic drugs or Digoxin.

What data supports the effectiveness of the drug mirabegron for treating overactive bladder in older women?

Research shows that mirabegron is effective in treating overactive bladder by relaxing the bladder muscle, which helps reduce the frequency of urination and urgency. It has been approved in multiple regions and is noted for having a better safety profile compared to older treatments. ^{1 2 3 4 5}

Is Mirabegron safe for treating overactive bladder in older women?

Mirabegron is generally well tolerated and has a good safety profile for treating overactive bladder, with side effects similar to a placebo in trials. It carries a low risk of causing heart rhythm changes and has fewer side effects like dry mouth compared to some other medications. ^{1 4 6 7 8}

How does the treatment of Mirabegron, Pelvic Floor Muscle Training, and Trospium Chloride for overactive bladder in older women differ from other treatments?

This treatment is unique because it combines a drug, Mirabegron, which relaxes the bladder muscle, with Pelvic Floor Muscle Training exercises that strengthen the muscles supporting the bladder, and Trospium Chloride, another medication that helps control bladder spasms. This combination targets both the physical and chemical aspects of overactive bladder, potentially offering a more comprehensive approach than using medication or exercises alone. ^{2 9 10 11 12}

Research Team

Steve Fisher

Principal Investigator

University of Texas Medical Branch at Galveston

Eligibility Criteria

This trial is for women aged 60 or older who can walk, have overactive bladder (OAB) or urinary incontinence, and are at high risk of falling. They must be able to consent, have tried lifestyle changes for their bladder condition, and have Medicare or private insurance. It excludes those with certain medical conditions like glaucoma, severe psychiatric issues, chronic liver/kidney diseases, or on conflicting medications.

Inclusion Criteria

I have a bladder control problem confirmed by a score or doctor's advice.

You answered "yes" to one of the questions on the 3-Key Questions form.

I am a woman aged 60 or older.

Exclusion Criteria

I am not planning any new treatments for overactive bladder in the next 6 months.

I have very high blood pressure that isn't controlled with medication.

I have a neurological condition like MS, Parkinson's, brain injury, dementia, or stroke that affects my bladder control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of three 12-week treatment arms: Pelvic Floor Muscle Training, Mirabegron, or Trospium Chloride

12 weeks

6 visits (in-person) for PFMT; medication adherence monitored for Mirabegron and Trospium

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of urinary incontinence and fall risk

6 months

Follow-up assessments at the end of the 12-week intervention and at 6 months

Treatment Details

Interventions

• Mirabegron
• Pelvic Floor Muscle Training
• Trospium Chloride

Trial Overview The study compares pelvic floor muscle training by physical therapists against two drug treatments—Mirabegron and Trospium Chloride—for managing OAB in older women prone to falls. Each participant will receive one treatment randomly for 12 weeks to assess the feasibility of a larger trial and impact on OAB symptoms.

Participant Groups

Group I: Pelvic Floor Muscle Training Experimental Treatment 1 Intervention

A 12-week, 6 visit, outpatient program of physical therapist delivered behavioral and pelvic floor muscle training (PFMT)

Group II: Mirabegron Active Control 1 Intervention

Individually titrated Mirabegron, starting at 25 mg daily and increased to 50 mg daily at 6-weeks, during the 12-week intervention period.

Group III: Trospium Chloride Active Control 1 Intervention

A 12-week course of Trospium -extended release, 60mg once daily.

Mirabegron is already approved in United States, European Union for the following indications:

Approved in United States as Myrbetriq for:

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

Approved in European Union as Mirabegron for:

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

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a study of 89 female patients with overactive bladder, treatment with 50 mg mirabegron once daily effectively reduced symptoms without significant differences compared to 0.1 mg imidafenacin taken twice daily.

Mirabegron was associated with fewer adverse events, particularly a lower incidence of dry mouth, compared to imidafenacin, making it a safer option for managing overactive bladder symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese female patients with overactive bladder: A randomized controlled trial (COMFORT study). Otsuka, A., Kageyama, S., Suzuki, T., et al.[2018]

Both solifenacin and mirabegron are effective in relieving symptoms of overactive bladder (OAB), with significant improvements in OABSS scores after 4 weeks of treatment in a study of 60 female patients.

Mirabegron is associated with fewer treatment-related side effects compared to solifenacin, suggesting it may be a better first-line treatment option for OAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison Of Solifenacin And Mirabegron For The Treatment Of Overactive Bladder. Jamil, MN., Irum, S., Islam, EU.[2023]

Mirabegron is an effective once-daily oral treatment for overactive bladder (OAB) that works by activating β3 adrenoceptors, leading to improved bladder filling and reduced urination frequency, with a better safety profile compared to traditional antimuscarinic drugs.

The drug is generally well tolerated, with common side effects including hypertension and urinary tract infections, and its pharmacokinetics can vary based on dose and gender, which may have implications for cardiovascular safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. Kashyap, M., Tyagi, P.[2013]

Mirabegron is the first beta-3 adrenergic agonist approved for treating overactive bladder (OAB), showing efficacy in reducing symptoms like urge incontinence and urinary frequency in both men and women.

The drug has a favorable safety profile, lacking the common side effects associated with traditional anticholinergic treatments, making it a suitable option for patients who did not respond to those medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[MIRABEGRON--A NEW DRUG FOR TREATMENT OF OVERACTIVE BLADDER]. Kasjan, GR.[2015]

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]

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 study of 50 sexually active women with overactive bladder (OAB), treatment with Mirabegron for 12 weeks significantly improved OAB symptoms, with 59.5% achieving complete urinary continence.

Mirabegron also led to a notable enhancement in female sexual function, with 84% of participants showing improved scores on the Female Sexual Function Index, and 32% reporting no sexual dysfunction after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of Mirabegron on sexual function in women with idiopathic overactive bladder. Gubbiotti, M., Giannantoni, A., Cantaluppi, S., et al.[2020]

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]

A systematic review of 99 studies found that various nonantimuscarinic treatments, including pelvic floor muscle exercises, botulinum toxin A, and mirabegron, are effective in improving symptoms of overactive bladder, such as urgency and incontinence.

Pelvic floor exercises, especially when combined with biofeedback, showed significant improvements in both subjective and objective outcomes, while treatments like sacral neuromodulation were found to be more effective than traditional antimuscarinic medications for enhancing quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonantimuscarinic treatment for overactive bladder: a systematic review. Olivera, CK., Meriwether, K., El-Nashar, S., et al.[2021]

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]

In a study of 77 women with overactive bladder (OAB), pelvic floor physical therapy (PFPT) led to a reported improvement in symptoms for 71.4% of patients, with better outcomes associated with attending more sessions.

Patients who received myofascial release techniques during PFPT showed a significantly higher improvement rate of 84.7%, compared to only 27.8% for those who did not receive this treatment, highlighting the importance of myofascial release in therapy for OAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consideration of pelvic floor myofascial release for overactive bladder. Wolff, BJ., Joyce, CJ., McAlarnen, LA., et al.[2021]

Mirabegron is as effective as traditional antimuscarinic agents for treating overactive bladder (OAB), based on a meta-analysis of 10 clinical trials involving 12-week treatment periods.

For patients at risk of cognitive issues or with certain conditions, starting treatment with mirabegron (at 25 mg or 50 mg) may be safer than antimuscarinics, especially in elderly patients or those with urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to choose appropriate medication for overactive bladder: Findings from the largest integrated clinical trial database analysis of mirabegron studies. Kuo, HC.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese female patients with overactive bladder: A randomized controlled trial (COMFORT study). [2018]

2. Pakistan pubmed.ncbi.nlm.nih.gov

Comparison Of Solifenacin And Mirabegron For The Treatment Of Overactive Bladder. [2023]

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

The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. [2013]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[MIRABEGRON--A NEW DRUG FOR TREATMENT OF OVERACTIVE BLADDER]. [2015]

5. 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]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. 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]

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

Nonantimuscarinic treatment for overactive bladder: a systematic review. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

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

Consideration of pelvic floor myofascial release for overactive bladder. [2021]

12. India pubmed.ncbi.nlm.nih.gov

How to choose appropriate medication for overactive bladder: Findings from the largest integrated clinical trial database analysis of mirabegron studies. [2022]