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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether sildenafil, commonly used for erectile dysfunction, can reduce urine leakage in people with spinal cord injuries. Participants will take both the actual medication and a placebo (a harmless pill with no active drug) at different times to assess effectiveness. Ideal participants are adults with a spinal cord injury who experience urinary incontinence at least three times a week and are dissatisfied with their current situation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, giving participants a chance to contribute to important medical advancements.

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).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that sildenafil citrate is usually well-tolerated. The FDA has approved it for treating erectile dysfunction, indicating its safety for that use. However, it may not be safe for all conditions.

In studies with sildenafil, some participants experienced mild side effects such as headaches, skin redness, and indigestion. These side effects did not differ significantly from those experienced by participants taking a placebo, suggesting they might be similar to taking an inactive substance.

For those considering joining this trial, it is helpful to know that many people have safely used sildenafil for other purposes. However, discussing any concerns with a doctor is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for urinary incontinence?

Researchers are excited about Sildenafil for urinary incontinence because it offers a unique approach compared to standard treatments like pelvic floor exercises, medications such as anticholinergics, or even surgery. Unlike these options, Sildenafil, commonly known by its brand name Viagra, works by enhancing blood flow and relaxing smooth muscles. This mechanism, which is different from traditional treatments that primarily target bladder control, could potentially reduce symptoms more effectively and with fewer side effects. Additionally, the rapid action of Sildenafil might provide quicker relief for patients experiencing this condition.

What evidence suggests that sildenafil might be an effective treatment for urinary incontinence in patients with spinal cord injuries?

Research suggests that sildenafil might help with urinary incontinence by improving blood flow and muscle strength. Some studies have shown it can help with urinary symptoms, but not all agree. One study found that people taking sildenafil experienced better urinary function after prostate surgery. However, another study found no significant difference between sildenafil and a placebo for urinary symptoms. In this trial, participants will receive either sildenafil or a placebo in different sequences to evaluate its effects. Overall, sildenafil's ability to improve blood flow and possibly strengthen muscles supports its potential to help with urinary issues. ^{1 2 3 6 7}

Who Is on the Research Team?

Kathy Vincent, MD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

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 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.

Willing and able to provide written informed consent

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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]

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]

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 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]

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 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 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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17296414/

Sildenafil citrate improves erectile function and urinary ... Daily dosing with sildenafil may improve lower urinary tract symptoms. However, the lack of effect on urinary flow rates may mean that a new basic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04565925

Sildenafil for Treatment of Urinary Incontinence in Patients ... Results will be reported as mL urine remaining. after 4 weeks of sildenafil treatment. Post void residual urine volume as measured by ultrasound bladder scanner ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4707894/

Nightly sildenafil use after radical prostatectomy has ... In a randomized controlled study, nightly use of sildenafil was associated with decreased urinary function scores using the EPIC questionnaire.

4. europeanurology.com europeanurology.com/article/S0302-2838(06)00704-4/pdf

Results of Double-Blind Placebo-Controlled ... Results: No statistical significant difference was seen in any voiding parameters and diaries when sildenafil citrate was compared with placebo.

5. withpower.com withpower.com/trial/phase-1-urinary-incontinence-2-2017-d4943

Sildenafil for Urinary Incontinence · Info for Participants Sildenafil has been shown to improve blood flow as well as muscle mass and strength and to decrease muscle fatigue. The investigators believe that it will ...

6. withpower.com withpower.com/trial/phase-3-enuresis-7-2021-a2d49

Sildenafil for Urinary Incontinence The goal of this study is to determine whether administration of sildenafil will decrease urine leakage in patients with spinal cord injuries. Show more. Will I ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/20895s039s042lbl.pdf

Label: VIAGRA (sildenafil citrate) tablets - accessdata.fda.gov There are no controlled clinical data on the safety or efficacy of VIAGRA in the following groups; if prescribed, this should be done with caution ...