Sildenafil for Urinary Incontinence

Recruiting at 1 trial location

Overseen By Kathy Vincent, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Nitrates, Steroids, PDE5 inhibitors, others

Disqualifiers: Multiple sclerosis, Heart disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to determine whether administration of sildenafil will decrease urine leakage in patients with spinal cord injuries.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not use systemic nitrates, anabolic steroids, corticosteroids, or long-acting PDE5 inhibitors for 1 month, short-acting PDE5 inhibitors for 1 week, and alpha blockers, anticholinergic agents, bethanechol, or other urinary incontinence treatments for 2 weeks (3 weeks for long-acting muscarinic receptor antagonists).

What data supports the effectiveness of the drug Sildenafil Citrate for urinary incontinence?

Research on similar drugs like tadalafil, which is also used for urinary symptoms, shows that it can improve lower urinary tract symptoms in men. This suggests that Sildenafil Citrate might have similar effects, although direct evidence for urinary incontinence is not provided. ^{1 2 3 4 5}

Is sildenafil generally safe for humans?

Sildenafil has been studied in over 16,000 men for erectile dysfunction, showing it is generally safe with some common side effects like headaches and flushing. It has been used widely in general practice, and while it is mostly safe, some people may experience adverse reactions, especially if they have other health conditions. ^{6 7 8 9 10}

How does the drug Sildenafil Citrate differ from other drugs for urinary incontinence?

Sildenafil Citrate, commonly known for treating erectile dysfunction, is being explored for urinary incontinence, which is unique as it primarily works by increasing blood flow and relaxing muscles, unlike other treatments that focus on strengthening the urethral sphincter or altering neurotransmitter levels. ^{11 12 13 14 15}

Research Team

Kathy Vincent, MD

Principal Investigator

University of Texas

Eligibility Criteria

This trial is for adults aged 18-75 with spinal cord injuries who experience urinary incontinence, having at least three leakage episodes per week. Participants must have a urodynamics assessment and be willing to follow study procedures. Excluded are those satisfied with their current quality of life due to urinary symptoms, using certain medications or treatments recently, pregnant or lactating women, and individuals with significant health issues like heart disease or active cancer.

Inclusion Criteria

I am between 18 and 75 years old with a spinal cord injury.

I experience urinary leaks at least 3 times a week.

I have had a bladder function test in the last 3 years or can have one before the study starts.

Exclusion Criteria

I have had more than 4 urinary tract infections in a year.

I have a serious heart, liver, kidney, lung, blood, autoimmune or circulation condition.

My blood pressure is within the safe range for sildenafil use.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a double-blinded randomized crossover treatment of sildenafil and placebo, each for 4 weeks with a 2-week washout period in between

10 weeks

Multiple visits for assessments and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Sildenafil Citrate

Trial Overview The study aims to see if sildenafil can reduce urine leakage in patients with spinal cord injuries compared to a placebo. It's designed as an experiment where participants don't know if they're getting the actual drug or a dummy pill (placebo).

Participant Groups

Group I: Sildenafil 20mg TID then Placebo TID Experimental Treatment 2 Interventions

Subjects will be administered Sildenafil 20mg TID for 4 weeks. There will be a 2 week washout period then subjects will be administered Placebo (lactose) TID for 4 weeks.

Group II: Placebo TID then Sildenafil 20mg TID Experimental Treatment 2 Interventions

Subjects will be administered Placebo (lactose) TID for 4 week. There will be a 2 week washout period and then subjects will be administered Sildenafil 20mg TID for 4 weeks.

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

Findings from Research

In a study of 126 men with non-neurogenic detrusor underactivity, both tadalafil and silodosin significantly improved lower urinary tract symptoms and voiding functions over 12 months.

Tadalafil was found to be more effective than silodosin, showing greater improvements in maximum urinary flow rate (3.0 mL/s vs. 1.7 mL/s) and bladder contractility index (from 77.9 to 97.6 vs. 80.0 to 86.1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tadalafil versus silodosin on voiding function in male patients with non-neurogenic detrusor underactivity: A comparative study using propensity score matching. Matsukawa, Y., Majima, T., Funahashi, Y., et al.[2021]

In a study of 102 men with post-micturition dribble (PMD), taking tadalafil 5 mg daily significantly improved PMD symptoms and reduced PMD volume compared to a placebo over 12 weeks, with 68.8% of tadalafil users reporting symptom improvement.

Tadalafil was well-tolerated, with no serious adverse events reported, indicating it is a safe and effective treatment option for PMD in men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tadalafil 5 mg on post-micturition dribble in men with lower urinary tract symptoms: a multicentre, double-blind, randomized, placebo-controlled trial. Yang, DY., Jeong, HC., Ko, K., et al.[2020]

In a multicenter trial involving 200 men with moderate to severe lower urinary tract symptoms (LUTS), standardized urodynamic studies showed that daily tadalafil significantly improved urinary flow measures, demonstrating good test-retest reproducibility.

The study successfully reduced inter-site variability through centralized training and standardized procedures, resulting in a low rate of invalid studies (0.6% at endpoint) and strong correlation coefficients for key pressure-flow parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urodynamic standardization in a large-scale, multicenter clinical trial examining the effects of daily tadalafil in men with lower urinary tract symptoms with or without benign prostatic obstruction. Kraus, SR., Dmochowski, R., Albo, ME., et al.[2015]

Silodosin and tadalafil were found to be more effective than placebo in improving lower urinary tract symptoms (LUTS) in a review of 23 randomized controlled trials involving over 9000 participants, although they were associated with more adverse effects, such as abnormal ejaculation with silodosin.

Anticholinergic medications only showed effectiveness in improving LUTS when used in combination with an alpha-blocker, and overall evidence for other newer drugs was generally low strength or insufficient, highlighting the need for longer trials to better understand their long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review. MacDonald, R., Brasure, M., Dahm, P., et al.[2019]

In a 12-week study involving 511 men with lower urinary tract symptoms, tadalafil significantly improved treatment satisfaction compared to placebo, particularly in terms of perceived efficacy and overall satisfaction.

Tamsulosin did not show a significant difference in treatment satisfaction compared to placebo, indicating that tadalafil may be a more favorable option for men with benign prostatic hyperplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomised, placebo-controlled study. Oelke, M., Giuliano, F., Baygani, SK., et al.[2022]

The new sildenafil spray demonstrated equivalent bioavailability to the traditional tablet form, but it allowed for a faster onset of action, with maximum concentration reached in 51 minutes compared to 62 minutes for the tablet.

Most adverse events reported during the studies were mild to moderate, indicating that the new spray form is generally safe for use in healthy male volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic features of sildenafil spray in healthy men depending on food intake]. Krivoborodov, GG., Zakharov, KA., Vasilyuk, VB., et al.[2022]

A large observational study involving 22,471 patients found that sildenafil, used primarily for erectile dysfunction, has a safety profile consistent with expectations, with no unexpected adverse drug reactions reported.

The study showed that the standardized mortality ratio for deaths due to ischemic heart disease in patients taking sildenafil was not higher than that of the general male population in England, indicating no increased risk associated with the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of sildenafil for male erectile dysfunction: experience gained in general practice use in England in 1999. Boshier, A., Wilton, LV., Shakir, SA.[2015]

Sildenafil has been extensively evaluated in over 74 clinical trials involving more than 16,000 men with erectile dysfunction, demonstrating its efficacy and safety across diverse patient populations.

The review addresses concerns among urologists regarding the use of sildenafil in patients with multiple health conditions, highlighting the importance of understanding potential risks, including self-discontinuation of therapy and the dangers of counterfeit medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Contemporary aspects of using sildenafil]. Efremov, EA., Kasatonova, EV., Melnik, YI., et al.[2017]

In a 12-week study involving 329 men with erectile dysfunction, 74% of those treated with 50 mg sildenafil reported improved erections, compared to only 16% in the placebo group, demonstrating its high efficacy (p < 0.0001).

Sildenafil was well-tolerated, with common side effects like headache and flushing being mild to moderate, and less than 1% of participants discontinued treatment due to adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Sildenafil Study Group. Padma-Nathan, H., Steers, WD., Wicker, PA.[2015]

Sildenafil citrate (Viagra) is an effective oral treatment for erectile dysfunction (ED) across various causes, including organic and psychogenic factors, and has revolutionized ED management since its introduction.

The review highlights sildenafil's safety profile, particularly its cardiovascular benefits, and discusses its effectiveness in special populations, such as men with diabetes or those who have undergone prostate surgery, emphasizing its broad applicability and positive impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sildenafil in erectile dysfunction: a critical review. Salonia, A., Rigatti, P., Montorsi, F.[2019]

In a study involving 16 healthy women, the selective serotonin 5-HT2c receptor agonist ASP2205 did not increase urethral pressure, indicating it may not be effective for treating stress urinary incontinence.

Duloxetine, on the other hand, significantly increased urethral pressure and was better tolerated than ASP2205, which caused more central nervous system-related side effects, especially at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. Klarskov, N., Van Till, O., Sawyer, W., et al.[2020]

In a study of 43 women with stress urinary incontinence, treatment with phenylpropanolamine (Rinexin) significantly improved subjective symptoms compared to placebo, with 15 out of 21 women reporting clinical improvement.

Rinexin also led to a significant 14% increase in maximum urethral closure pressure (MUCP), particularly in women with grade I incontinence, while showing a good safety profile with rare adverse effects and no changes in blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of phenylpropanolamine on female stress urinary incontinence. Lehtonen, T., Rannikko, S., Lindell, O., et al.[2013]

Stress urinary incontinence (SUI) is a prevalent issue among women, accounting for up to 78% of all incontinence cases, yet there are currently no approved pharmacological treatments specifically for SUI.

Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has shown significant efficacy in reducing urinary incontinence episodes and improving quality of life in women with SUI in randomized, placebo-controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of stress incontinence]. Jost, WH., Marsalek, P., Michel, MC.[2022]

Duloxetine is the only widely approved medication for treating stress urinary incontinence (SUI) in women, working by increasing serotonin and noradrenalin levels to enhance the activity of the external urethral sphincter, thereby preventing urine leakage.

Recent studies have shown that duloxetine significantly affects the excitability of pudendal motor neurons and increases sphincter contractility, supporting its mechanism of action in enhancing urethral closure during the storage phase of urination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What do we know about duloxetine's mode of action? Evidence from animals to humans. Schuessler, B.[2022]

Duloxetine, at a dosage of 80 mg per day, significantly reduced the frequency of incontinence episodes and improved quality of life in women with stress urinary incontinence, as shown in multiple phase 2 and phase 3 clinical trials across five continents involving diverse patient populations.

The treatment was generally well-tolerated, with nausea being the most common side effect, which was mostly mild and resolved within a few weeks, indicating that duloxetine is a promising option for managing stress urinary incontinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine: a new approach for treating stress urinary incontinence. Moore, K.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Effects of tadalafil versus silodosin on voiding function in male patients with non-neurogenic detrusor underactivity: A comparative study using propensity score matching. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Effect of tadalafil 5 mg on post-micturition dribble in men with lower urinary tract symptoms: a multicentre, double-blind, randomized, placebo-controlled trial. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Urodynamic standardization in a large-scale, multicenter clinical trial examining the effects of daily tadalafil in men with lower urinary tract symptoms with or without benign prostatic obstruction. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomised, placebo-controlled study. [2022]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic features of sildenafil spray in healthy men depending on food intake]. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of sildenafil for male erectile dysfunction: experience gained in general practice use in England in 1999. [2015]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Contemporary aspects of using sildenafil]. [2017]

9. India pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Sildenafil Study Group. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Sildenafil in erectile dysfunction: a critical review. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. [2020]

12. Finland pubmed.ncbi.nlm.nih.gov

The effect of phenylpropanolamine on female stress urinary incontinence. [2013]

13. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of stress incontinence]. [2022]

14. England pubmed.ncbi.nlm.nih.gov

What do we know about duloxetine's mode of action? Evidence from animals to humans. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Duloxetine: a new approach for treating stress urinary incontinence. [2022]