Clinical trial NCT02916693: Mirabegron For Erectile Dysfunction
Official title: Mirabegron For Erectile Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Erectile Dysfunction
Overactive Bladder
Urinary Incontinence
Keywords: Mirabegron
Overactive Bladder
Erectile Dysfunction
Beta 3 agonist
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma US, Inc.
First posted: 2016-09-27
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The only class of oral erectile dysfunction (ED) medication on the market are the phosphodiesterase Type 5 inhibitors (PDE5i). This pilot study is being done to evaluate the effect of Mirabegron, an oral beta-3 adrenergic agonist, on men with both Overactive Bladder (OAB) symptoms and mild to moderate ED.

Detailed description: ED affects up to 30 million men in the United States. The only class of oral medication approved for ED is PDE5i. These include sildenafil, tadalafil, vardenafil and avanafil. Other pharmacologic options in the treatment of ED are delivered as an intraurethral suppository (alprostadil) or intracavernosal injection (alprostadil, papaverine, phentolamine, atropine). These are more invasive routes of administration. Men who fail to obtain benefit from a PDE5i or those who have a contraindication to this class of medication may ultimately avoid further pharmacologic treatment options. An alternative class of oral medication to treat ED may prove to be of benefit to a large population of underserved men.

There is in vitro evidence that beta-3 adrenergic receptors exist in human corpus cavernosum tissue. Activation of these receptors results in vasorelaxation, suggesting a potential pro-erectogenic effect is possible in vivo. Additionally, nebivolol, a beta-blocker, has pro-erectogenic effects noted in several studies. There is evidence that nebivolol exerts beta-3 adrenergic agonism, which may explain the mechanism by which these effects occur.

Mirabegron is the only available beta-3 adrenergic agonist in the United States. Its favorable safety profile and the potential for therapeutic efficacy in ED make it suitable for further investigation.

It is hypothesized that beta-3 adrenergic activation offers a pharmacologic target for the treatment of ED. Men with mild, mild to moderate, or moderate ED and symptoms of OAB can be recruited with pre- and post- Mirabegron administration assessment of their ED to determine the validity of this hypothesis. Men with severe ED will be excluded as historical data shows they are less likely to benefit from oral pharmacologic therapy alone. Mirabegron is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with OAB.

Eligibility criteria: Inclusion Criteria:

* presence of mild ED \[Erectile Function domain of the International Index of Erectile Function (IIEF EF) score 22-25\], mild to moderate ED (IIEF EF domain score 17-21) or moderate ED (IIEF EF domain score 11-16)
* presence of OAB symptoms for at least 3 months
* at least 3 micturitions per day
* at least 3 episodes of urgency in a 3 day period

Exclusion Criteria:

* history of pelvic surgery
* concurrent ED therapy
* history of penile surgery
* history of priapism (unwanted, prolonged painful erection)
* history of neurologic disease
* uncontrolled hypertension: systolic blood pressure (BP) \> 140 mmHg or diastolic BP \> 90 mmHg
* Stage 4 or 5 chronic kidney disease, Creatinine clearance rate \< 30ml/min
* moderate or severe hepatic impairment
* concomitant use of CYP2D6-metabolized drugs or digoxin
* post void residual greater than 150 ml
* evidence of urinary tract infection on urinalysis and/or urine culture

Primary outcomes:
measure: Erectile Function Assessed by IIEF Questionnaire
timeFrame: Baseline
measure: Erectile Function Assessed by IIEF Questionnaire
timeFrame: Week 2
measure: Erectile Function Assessed by IIEF Questionnaire
timeFrame: Week 4
measure: Erectile Function Assessed by IIEF Questionnaire
timeFrame: Week 8
measure: Erectile Function Assessed by IIEF Questionnaire
timeFrame: Week 12
Secondary outcomes:
measure: Health Related Quality of Life as Assessed by the OAB Questionnaire
timeFrame: Baseline
measure: Health Related Quality of Life as Assessed by the OAB Questionnaire
timeFrame: Week 2
measure: Health Related Quality of Life as Assessed by the OAB Questionnaire
timeFrame: Week 4
measure: Health Related Quality of Life as Assessed by the OAB Questionnaire
timeFrame: Week 8
measure: Health Related Quality of Life as Assessed by the OAB Questionnaire
timeFrame: Week 12
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institutions
state: Maryland
Study officials:
affiliation: Johns Hopkins, School of Medicine
name: Arthur L Burnett, M.D., M.B.A.
role: PRINCIPAL_INVESTIGATOR
References: