Mirabegron For Erectile Dysfunction

Phase 1

Completed

Conditions: Erectile Dysfunction
Overactive Bladder
Urinary Incontinence

Interventions: Drug: Mirabegron

Registration Number: NCT02916693

Lead Sponsor: Johns Hopkins University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 20

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mirabegron	Mirabegron	Participants take 25- 50mg oral Mirabegron tablets daily for 12 weeks,

Primary Outcome Measures

Name	Time	Method
Erectile Function Assessed by IIEF Questionnaire	Week 12	The International Index for Erectile Function (IIEF) questionnaire will be administered. This is a 15 item tool; 6 ask questions addressing Erectile function. Scores from 0-30 can be obtained in this domain. Scores are interpreted as follows: 0-6 = Severe dysfunction, 7-12 = Moderate dysfunction, 13-18 = mild-moderate dysfunction, 19-24 = mild dysfunction, 25-30 = No dysfunction.

Secondary Outcome Measures

Name	Time	Method
Health Related Quality of Life as Assessed by the OAB Questionnaire	Week 12	The Overactive Bladder questionnaire (OAB-q) health-related quality of life (HRQL) form will be administered. It is a 13 item tool assessing the health-related quality of life (HRQL) impact of OAB. Scores range from 13 to 78 with higher scores indicating a greater degree of a lower quality of life due to OAB.