Mirabegron + Behavioral Therapy for Parkinson's Disease

(SQUARE PD Trial)

Not yet recruiting at 2 trial locations

Overseen By Taressa Sergent

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Bladder relaxants

Disqualifiers: Cognitive impairment, Depression, Diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to find better treatments for overactive bladder symptoms in individuals with Parkinson's Disease. It evaluates whether combining two treatments—exercise-based behavioral therapy and the medication mirabegron, which relaxes bladder muscles—works better than each treatment alone. Participants will begin with either the medication or the exercise therapy, and if that proves ineffective, they will try both together. Suitable candidates have Parkinson’s and frequently experience urgent or frequent urination issues without infections. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping researchers understand its benefits for more patients.

Do I need to stop my current medications to join the trial?

You may need to stop taking a bladder relaxant for one week before joining the trial. If you're on a diuretic, alpha-blocker, dutasteride, or finasteride, your dose should be stable for a certain period before joining. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What is the safety track record for these treatments?

Studies have shown that mirabegron is generally safe for people with Parkinson's disease who have overactive bladder symptoms. One study found that about 50% of patients noticed symptom improvement after six weeks of taking mirabegron. Only two mild side effects were reported, indicating the drug is well-tolerated.

Another source reviewed FDA reports and identified some side effects, such as irregular heartbeat and palpitations, but these were uncommon. Most participants in these studies handled the treatment well.

In contrast, exercise-based behavioral therapy, which includes pelvic muscle exercises and bladder training, usually has even fewer side effects. Some research suggests it is as effective as drug treatments but without the risk of medication side effects.

Both treatments have been tested in people with Parkinson's, providing data on their safety. This information may help prospective trial participants feel more confident about the options. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining Mirabegron with exercise-based behavioral therapy for Parkinson's disease because this approach addresses both medication and lifestyle. Mirabegron, a beta-3 adrenergic agonist, targets bladder muscle relaxation, which may help with urinary symptoms common in Parkinson's patients. The unique combination with behavioral therapy offers a holistic approach, potentially enhancing the overall quality of life by tackling both the physical and lifestyle aspects of managing symptoms. This dual strategy might offer a more comprehensive solution compared to standard treatments that typically focus on one aspect alone.

What evidence suggests that this trial's treatments could be effective for overactive bladder symptoms in Parkinson's Disease?

Research has shown that mirabegron effectively treats overactive bladder symptoms in people with Parkinson's disease. Studies have found it improves bladder control and is safe to use. Mirabegron relaxes the bladder muscles, reducing the frequent urge to urinate. In this trial, some participants will receive mirabegron as part of the drug therapy group.

Behavioral therapy, such as pelvic floor exercises and bladder training, also effectively manages these symptoms. It can be as helpful as medication and has fewer side effects. Participants in this trial may receive exercise-based behavioral therapy as part of the behavioral therapy group. Both mirabegron and behavioral therapy offer promising options for improving bladder control in people with Parkinson's. ^{1 3 4 6 7}

Who Is on the Research Team?

Elizabeth Camille Vaughan, MD MS

Principal Investigator

Atlanta VA Medical and Rehab Center, Decatur, GA

Are You a Good Fit for This Trial?

This trial is for people with Parkinson's Disease who have significant symptoms of an overactive bladder, as indicated by a specific symptom score. Participants must be diagnosed by a specialist neurologist and not have severe cognitive impairment, intensive prior pelvic training, major depression, certain urinary conditions or sensitivities to the study drug.

Inclusion Criteria

I have been diagnosed with Parkinson's disease by a specialist.

My bladder control symptoms are severe, scoring 7 or more.

Exclusion Criteria

Significant cognitive impairment indicated by a Montreal Cognitive Assessment (MoCA) score of < 18 or a telephone-MoCA score < 13

Previous intensive pelvic floor muscle exercise training

Clinically significant depression as measured by a Geriatric Depression Scale-Short Form score of 10 or higher

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either drug therapy with mirabegron or exercise-based behavioral therapy

6 weeks

2 visits (in-person)

Re-randomization and Combination Treatment

Non-responders to initial treatment are re-randomized to receive combination therapy

6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise-based behavioral therapy
• Mirabegron

Trial Overview The study is testing if mirabegron (a drug) or exercise-based behavioral therapy can help with overactive bladder in Parkinson's patients. If one doesn't work alone, they'll try combining them. The trial also looks at what factors affect treatment response.

How Is the Trial Designed?

Group I: Combined Drug and Behavioral Therapy Group Active Control 2 Interventions

At 6 weeks post-randomization, participants will complete the ICIQ-OAB questionnaire. Participants reporting less than 2 points reduction will be re-randomized to either continue their initial treatment assignment or receive combination therapy by adding the alternate treatment strategy, thus participants initially treated with mirabegron will add behavioral therapy and participants initially treated with behavioral therapy will add mirabegron.

Group II: Drug Therapy Group Active Control 1 Intervention

Participants who are randomized to drug therapy will receive mirabegron 25mg at visit 2 (randomization visit).

Group III: Behavioral Therapy Group Active Control 1 Intervention

Participants who are randomized to exercise-based behavioral therapy will receive a comprehensive training program administered individually by a trained nurse practitioner interventionist to address urinary incontinence and other lower urinary tract symptoms.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6660386/

Behavioral therapy for urinary symptoms in Parkinson's ... Behavioral therapy included pelvic floor muscle exercises, bladder training, fluid and constipation management. Both groups completed bladder diary self- ...

2. neurology.org neurology.org/doi/10.1212/WNL.0b013e318219fab3

Behavioral therapy to treat urinary incontinence in ... This study provides Class IV evidence that exercise-based, biofeedback-assisted behavioral intervention can reduce UI frequency in patients >50 years old with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07187466

Sequential Multiple Assignment Randomized Trial to Treat ... The purpose of this study is to learn about different treatments for overactive bladder symptoms in Parkinson's Disease.

4. jwatch.org jwatch.org/na59274/2025/09/26/behavioral-therapy-overactive-bladder-patients-with

Behavioral Therapy for Overactive Bladder in Patients with ... Behavioral therapy was as effective as drug therapy, with fewer side effects. Patients with Parkinson disease often develop symptoms related to ...

5. jamanetwork.com jamanetwork.com/journals/jamaneurology/article-abstract/2836067

Behavioral Compared With Drug Therapy for Overactive ... Meaning Results of this study suggest that behavioral therapy is an effective treatment option for persons with PD, and fall risk should be ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00866710

Behavioral Therapy to Treat Urinary Incontinence in ... Behavioral Therapy to Treat Urinary Incontinence in Parkinson's Disease (BETTUR PD) ; ClinicalTrials.gov ID NCT00866710 ; Sponsor Atlanta VA ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772973724001553

Conservative management for urinary incontinence in ... This systematic review was conducted based on the data ... Behavioral therapy for urinary symptoms in parkinson's disease: A randomized clinical trial.