Erectile Dysfunction, Overactive Bladder, Urinary Incontinence
Conditions
Keywords
Mirabegron, Overactive Bladder, Erectile Dysfunction, Beta 3 agonist
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.
Interventions
DRUGMirabegron
FDA-approved, beta 3 agonist for over active bladder
Sponsors
Astellas Pharma US, Inc.
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Erectile Function Assessed by IIEF Questionnaire | Baseline | 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
| Measure | Time frame | Description |
|---|---|---|
| Health Related Quality of Life as Assessed by the OAB Questionnaire | Baseline | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirabegron 25 mg to 50 mg Treatment Single-center, non-randomized, single-arm study Participants received Mirabegron 25 mg for 2 weeks and switched to the 50 mg for 10 weeks | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 7 |
Baseline characteristics
| Characteristic | Mirabegron 25 mg to 50 mg Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 60.2 years STANDARD_DEVIATION 6.82 |
| Co-morbidities Cardiovascular disease | 2 Participants |
| Co-morbidities Diabetes Mellitus | 2 Participants |
| Co-morbidities Hyperlipidemia | 8 Participants |
| Co-morbidities Hypertension | 8 Participants |
| Erectile Dysfunction (ED) Severity Mild | 3 Participants |
| Erectile Dysfunction (ED) Severity Mild to moderate | 6 Participants |
| Erectile Dysfunction (ED) Severity Moderate | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
| Smoking History Current Smoker | 3 Participants |
| Smoking History Ex-smoker | 7 Participants |
| Smoking History Never Smoker | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 5 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Erectile Function Assessed by IIEF Questionnaire
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Erectile Function Assessed by IIEF Questionnaire | 12.7 score on a scale | Standard Deviation 5.4 |
Primary
Erectile Function Assessed by IIEF Questionnaire
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.
Time frame: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Erectile Function Assessed by IIEF Questionnaire | 13.8 score on a scale | Standard Deviation 5.1 |
Primary
Erectile Function Assessed by IIEF Questionnaire
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.
Time frame: Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Erectile Function Assessed by IIEF Questionnaire | 15.3 score on a scale | Standard Deviation 4.2 |
Primary
Erectile Function Assessed by IIEF Questionnaire
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.
Time frame: Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Erectile Function Assessed by IIEF Questionnaire | 17.8 score on a scale | Standard Deviation 7.9 |
Primary
Erectile Function Assessed by IIEF Questionnaire
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.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Erectile Function Assessed by IIEF Questionnaire | 15.8 score on a scale | Standard Deviation 6.9 |
Secondary
Health Related Quality of Life as Assessed by the OAB Questionnaire
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Health Related Quality of Life as Assessed by the OAB Questionnaire | 35.3 score on a scale | Standard Deviation 13.6 |
Secondary
Health Related Quality of Life as Assessed by the OAB Questionnaire
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.
Time frame: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Health Related Quality of Life as Assessed by the OAB Questionnaire | 30.7 score on a scale | Standard Deviation 11.4 |
Secondary
Health Related Quality of Life as Assessed by the OAB Questionnaire
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.
Time frame: Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Health Related Quality of Life as Assessed by the OAB Questionnaire | 30. score on a scale | Standard Deviation 13.3 |
Secondary
Health Related Quality of Life as Assessed by the OAB Questionnaire
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.
Time frame: Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Health Related Quality of Life as Assessed by the OAB Questionnaire | 26.9 score on a scale | Standard Deviation 10.6 |
Secondary
Health Related Quality of Life as Assessed by the OAB Questionnaire
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.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Health Related Quality of Life as Assessed by the OAB Questionnaire | 27.9 score on a scale | Standard Deviation 14.7 |