Sildenafil for Patent Foramen Ovale

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Oregon

Must not be taking: Sildenafil, Nitrates

Disqualifiers: Coronary artery disease, Pregnancy, others

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain types of diving affect the heart and blood flow in elite divers. It examines whether medications like sildenafil (commonly used to treat high blood pressure in the lungs) can help manage diving-induced blood pressure changes. Participants will receive either sildenafil or a placebo to assess the impact on blood flow during dives. Ideal candidates are elite breath-hold or experienced SCUBA divers living near Split, Croatia, without heart conditions or specific medication restrictions. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a unique opportunity to contribute to pioneering medical insights.

Will I have to stop taking my current medications?

If you are taking medication or herbal supplements for heart or respiratory diseases, you must stop them for 48 hours before testing. Also, you cannot participate if you are taking sildenafil, nitrates, or similar products.

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

Research has shown that sildenafil, the treatment tested in this trial, is generally safe and well-tolerated. Various studies have consistently demonstrated its safety for adults. Sildenafil, often known by the brand name Revatio, is commonly used to treat certain types of high blood pressure and erectile dysfunction.

In this trial, participants will receive a dose of 50 mg. Previous studies found that sildenafil is well-tolerated at doses of 50 or 100 mg. Some individuals may experience side effects like headaches or flushing (a warm, red feeling in the face), but these are usually mild.

The FDA has already approved sildenafil for other conditions, indicating a known safety record. However, the safety of sildenafil has not been fully studied in individuals with certain conditions like bleeding disorders or active stomach ulcers. Participants with these health issues should discuss potential risks with their healthcare providers.

Overall, while sildenafil is generally safe, anyone considering joining the trial should consult their doctor to determine if it's appropriate for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sildenafil for pulmonary hypertension related to breath-hold and SCUBA diving because it offers a unique approach compared to traditional treatments. Unlike other treatments that might take a while to show effects, sildenafil works by rapidly relaxing and widening blood vessels, potentially offering quick relief. This action specifically targets the pulmonary vasculature, which could make it particularly effective for this condition. Additionally, its oral administration makes it convenient for users, differing from some existing treatments that might require more invasive methods.

What evidence suggests that sildenafil could be effective for reducing pulmonary arterial pressure in divers?

Research has shown that sildenafil, which participants in this trial may receive, can help lower high blood pressure in the lungs. One study found that it reduced the risk of death in adults with this condition. While sildenafil is mostly known for treating erectile dysfunction, it may also aid lung issues by relaxing blood vessels and improving blood flow. Although direct evidence for its use in divers is lacking, its mechanism suggests it might help with lung problems caused by diving. ^{6 7 8 9 10}

Who Is on the Research Team?

Andrew Lovering, PhD

Principal Investigator

University of Oregon

Are You a Good Fit for This Trial?

Inclusion Criteria

People who are exceptional at holding their breath while diving.

People who have gone scuba diving before.

You live close to Split, Croatia.

Exclusion Criteria

Currently taking medication or herbal supplement for any heart or respiratory disease that cannot be ceased for 48 hours prior to testing

Women who are pregnant or trying to become pregnant

You have had heart problems related to blockages in your arteries in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants receive either sildenafil or placebo to assess its effect on pulmonary arterial pressure and right heart function during breath-hold and SCUBA diving conditions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in pulmonary arterial pressure and right heart function post-intervention

1 hour

1 visit (in-person)

Data Analysis

Analysis of collected data to determine the relationship between PFO, IPAVA blood flow, and pulmonary arterial pressure

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sildenafil

How Is the Trial Designed?

Group I: Sildenafil administration Active Control 1 Intervention

Administration of 50mg sildenafil one time, one hour prior to measurements

Group II: Placebo administration Placebo Group 1 Intervention

Administration of 50mg placebo one time, one hour prior to measurements

Who Is Running the Clinical Trial?

University of Oregon

Lead Sponsor

Trials

91

Recruited

46,700+

Published Research Related to This Trial

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]

In a 12-week study involving 254 men with erectile dysfunction in Egypt and South Africa, sildenafil (Viagra) significantly improved the ability to achieve and maintain erections compared to placebo, with 74% of sildenafil users reporting improved erections versus 27% for placebo (P<0.0001).

Sildenafil was found to be well-tolerated, with common side effects including headache, dyspepsia, and flushing, confirming its efficacy and safety profile consistent with previous global studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa. Levinson, IP., Khalaf, IM., Shaeer, KZ., et al.[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) has been prescribed to over 10 million patients and has shown significant improvements in erectile function across various conditions, including diabetes and cardiovascular disease, based on clinical trials.

The medication is generally well-tolerated, with most side effects being mild or moderate and rarely causing patients to stop treatment, indicating its safety in a wide range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year update of sildenafil citrate (Viagra) efficacy and safety. Sadovsky, R., Miller, T., Moskowitz, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2387281/

Long-term safety and effectiveness of sildenafil citrate in ... The majority of men were satisfied with sildenafil treatment for their ED and reported improved ability to engage in sexual activity. Throughout the 4-year ...

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/211714

Sildenafil for Male Erectile Dysfunction: A Systematic ... The mean percentage of sexual intercourse attempts that were successful was 42% for men with ischemic heart disease receiving sildenafil vs 14% in those ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1874251/

Onset and duration of action of sildenafil for the treatment ... Sildenafil is an effective oral treatment for ED that produces a penetrative erection as early as 12 min and for most patients, within 30 min after dosing.

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.068107

Randomized, Multicenter Study to Assess the Effects of ... This study evaluated the effect of sildenafil on the risk of death in adults with pulmonary arterial hypertension at 3 dose levels: 5 mg, 20 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1743609516003209

Efficacy and Safety of Sildenafil by Age in Men With ... For men at least 75 years old, sildenafil treatment is associated with statistically significant and clinically meaningful improvements in erectile function.

6. revatio.com revatio.com/en/safety-info

important safety information and indication Never take REVATIO with any nitrate or guanylate cyclase stimulator medicines. Your blood pressure could drop quickly to an unsafe level. Nitrates include:.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/021845s025lbl.pdf

REVATIO (sildenafil) - accessdata.fda.gov Overall, the safety data for sildenafil 80 mg TID dose in Study A1481324 was consistent with the established safety profile of sildenafil in previous adult PAH ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/021845s011,022473s004,0203109s002lbl.pdf

REVATIO (sildenafil) Label - accessdata.fda.gov The safety of REVATIO is unknown in patients with bleeding disorders or active peptic ulceration. 5.5 Visual Loss. When used to treat erectile dysfunction, non- ...

9. fertstert.org fertstert.org/article/S0015-0282(02)04358-3/fulltext

Safety data for sildenafil As indicated by the authors, sildenafil (Viagra) is typically prescribed for men. As a result safety data for differing doses and for women is relatively ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2810448/

Safety of sildenafil citrate: review of 67 double-blind placebo ... Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged ≥ 65 years, and in those aged ≥ 75 years. Analyses of the ...