Comparative Study Between Behavior Therapy and Behavior Therapy Plus Mirabegron in Sexually Active Men With OAB Symptoms

Comparative Study Between Behavior Therapy and Behavior Therapy Plus Mirabegron 50mg in Sexually Active Men With Bothersome Overactive Bladder Symptoms - A Multicenter, Randomized Study

The objective of this study is to evaluate and compare the therapeutic effects on OAB symptoms, and sexual functions, in terms of erectile function and ejaculatory function, in sexually active OAB male treated with behavior therapy or behavior therapy plus Mirabegron (50 mg).

Overactive bladder (OAB) syndrome is a subset of storage-predominant lower urinary tract symptoms (LUTS) and has a significant impact on quality of life. Men with OAB generally experience a reduced quality of life, which may include a negative impact on sexual function. A previous study revealed that OAB is associated with erectile dysfunction (ED; prevalence odds ratio, 1.5; 95% confidence interval, 1.1-2.2) to a level comparable with that of hypertension or diabetes, both of which are known risk factors for ED. Furthermore, men with OAB were nine and seven times more likely to report diminished sexual enjoyment and decreased sexual activity, respectively, due to urinary symptoms than men without urinary symptoms.

Behavior therapies are designed as first- line treatment for the treatment of OAB with or without concomitant medication. Mirabegron, a selective β3 adrenoceptor agonist, is indicated for the treatment of OAB. Earlier research studying the role and distribution of β3-adrenoreceptors revealed that the receptors exert other physiological functions such as lipolysis and are present not only in adipose tissue but also in human gall bladder, colon, prostate, skeletal muscles and corpus cavernosum (CC) smooth muscles. It was found that activation by a selective experimental β3-receptor agonist, BRL 37344, elicited relaxation of human CC smooth muscle via a cGMP-dependent but NO-independent mechanism, leading to observable β3-receptor-mediated vasorelaxant tone of CC. The potential effect of β3-receptor agonism at human CC mediated by highly selective mirabegron in both human CC and rat CC that mirabegron markedly relaxed isolated CC strips by activating β3-adrenoceptors localized in cavernosal smooth muscle cells, independently of the NO-cGMP pathway. Recently, intra-cavernosal injection of mirabegron improved erectile function and neurogenic relaxation of corpus cavernosum in diabetic rats.

These early results have spurred research interest in mirabegron-induced CC relaxation and encouraged further clinical studies observing and evaluating the effect of mirabegron on male sexual function. Researchers at Johns Hopkins University has recently completed recruitment of a phase 1 interventional trial (NCT02916693) that aimed to address the hypothesis that activation of β3-adrenoceptors by mirabegron offers an alternative pharmacologic pathway for the treatment of erectile dysfunction. A preliminary small-scale prospective interventional study including 128 male LUTS patients treated with mirabegron 50 mg, 34 of whom had diagnosis of OAB and were sexually active, showed that mirabegron usage did not improve erectile function, as evaluated by International Index of Erectile Function (IIEF-5 4.9% decrease at 4-week; p = 0.106, and 9.1% decrease at 12-week follow-up; p = 0.077). However, the IIEF-5 was significantly decreased in the higher baseline IIEF-5 (≥17) group (11.7% decrease; p = 0.044), noncoronary artery disease (13.2%; p = 0.007) group and non-DM group (13.9% decrease; p = 0.021) at 12-week follow-up.

The accumulated research output warrants the initiation of a prospective study involving a larger patient cohort to evaluate the effect of mirabegron on male sexual function in addition to alleviate OAB symptoms. The objective of this study is to evaluate and compare the therapeutic effects on OAB symptoms, and sexual functions, in terms of erectile function and ejaculatory function, in sexually active OAB male treated with behavior therapy or behavior therapy plus Mirabegron (50 mg).

Inclusion Criteria:

• Sexually active men with OAB ≥ 20 years
• Diagnosed with OAB based on OABSS (OABSS urgency score of ≥2 and sum score of ≥3)
• Patients can sign informed consent and record voiding diary

Exclusion Criteria:

• Concurrent use of PDE5 inhibitor or testosterone therapy during study period
• History of stress urinary incontinence
• Neurologic conditions associated with OAB symptoms
• Evidence of active urinary tract infection or urinary tract stone at screening
• Confirmed or suspected genitourinary tract or pelvic malignancy
• Genitourinary tract operation during the 3-month period prior to baseline
• Postvoid residual urine volume (PVR) ≥ 100 mL
• History of uncontrolled hypertension (systolic >180 mmHg and/or diastolic >110 mmHg)
• History of intolerance to mirabegron
• History of medical conditions or presence of patient factors that, in the judgement of the investigator, would preclude adherence to study protocol
• Patient had received intravesical onabotulinumoxinA treatment within recent 6 months