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

Not Applicable
Completed
Conditions
Sexual Activity
Behavior Therapy
Sexual Behavior
Urinary Bladder, Overactive
Sexual Function Disturbances
Interventions
Behavioral: Behavior therapy alone
Registration Number
NCT04420533
Lead Sponsor
Chang Gung Memorial Hospital
Brief Summary

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).

Detailed Description

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
150
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Behavior therapy aloneBehavior therapy aloneBehavior therapy alone
Behavior therapy plus mirabegron 50mgBehavior therapy aloneBehavior therapy plus Betmiga prolonged-release tablets (mirabegron) 50mg QDAC PO
Behavior therapy plus mirabegron 50mgMirabegron 50 MG Extended Release Oral TabletBehavior therapy plus Betmiga prolonged-release tablets (mirabegron) 50mg QDAC PO
Primary Outcome Measures
NameTimeMethod
Change from baseline in OABSS at Week 12Baseline and Week 12

Change from baseline in OABSS (Overactive Bladder Symptom Score) at Week 12 (lower OABSS score represent a better outcome)

Change from baseline in IIEF-5 at Week 12Baseline and Week 12

Change from baseline in IIEF-5 (International Index of Erectile Function) at Week 12 (higher IIEF-5 score represent a better outcome)

Secondary Outcome Measures
NameTimeMethod
Change from baseline in MSHQ-EjD Short Form score at Week 4Baseline and Week 4

Change from baseline in MSHQ-EjD (Male Sexual Health Questionnaire -Ejaculatory Domain) Short Form score at Week 4 (higher MSHQ-EjD Short Form Q1-Q3 sum scores represent a better outcome; lowerer MSHQ-EjD Short Form Q4 score represent a better outcome)

Net change of Frequency episode, nocturia episode, urgency episode, UUI episodes in 3-day voiding diary from baseline to 1 and 3 months after the treatment dayBaseline, Week 4 and Week 12

Net change of Frequency episode, nocturia episode, urgency episode, UUI episodes in 3-day voiding diary from baseline to 1 and 3 months after the treatment day (lower episode represent a better outcome)

Change from baseline in MSHQ-EjD Short Form score at Week 12Baseline and Week 12

Change from baseline in MSHQ-EjD (Male Sexual Health Questionnaire -Ejaculatory Domain) Short Form score at Week 12 (higher MSHQ-EjD Short Form Q1-Q3 sum scores represent a better outcome; lower MSHQ-EjD Short Form Q4 score represent a better outcome)

Net change of voided volume from baseline to 1 and 3 months after the treatment dayBaseline, Week 4 and Week 12

Net change of voided volume from baseline to 1 and 3 months after the treatment day (higher voided volume represent a better outcome)

Change from baseline in OABSS at Week 4Baseline and Week 4

Change from baseline in OABSS (Overactive Bladder Symptom Score) at Week 12 (lower OABSS score represent a better outcome)

Net change of Qmax from baseline to 1 and 3 months after the treatment dayBaseline, Week 4 and Week 12

Net change of maximum flow rate (Qmax) from baseline to 1 and 3 months after the treatment day (higher Qmax and voided volume represent a better outcome)

Change from baseline in IIEF-5 at Week 4Baseline and Week 4

Change from baseline in IIEF-5 (International Index of Erectile Function) at Week 12 (higher IIEF-5 score represent a better outcome)

Net change of PVR volume from baseline to 1 and 3 months after the treatment dayBaseline, Week 4 and Week 12

Net change of postvoid residual (PVR) volume from baseline to 1 and 3 months after the treatment day (lower PVR represent a better outcome)

Net change of IPSS from baseline to 1 and 3 months after the treatment dayBaseline, Week 4 and Week 12

Net change of IPSS (International prostate symptom score) from baseline to 1 and 3 months after the treatment day (lower IPSS represent a better outcome)

Net change of PPBC score from baseline to 1 and 3 months after the treatment dayBaseline, Week 4 and Week 12

Net change of PPBC score (Patient perception of bladder condition) from baseline to 1 and 3 months after the treatment day (lower PPBC represent a better outcome)

Net changes of the GRABaseline, Week 4 and Week 12

Global response assessment (GRA) of satisfaction by the patient (categorized into -3, -2, -1, 0, 1, 2, 3, indicating markedly worse to markedly improved) at 1 and 3 months after the treatment day. An improvement of GRA by 2 scales is considered effective.

Trial Locations

Locations (1)

Chang Gung Memorial Hospital, Chang Gung University College of Medicine

🇨🇳

Kaohsiung, Taiwan

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