Bosentan for Stress-Related High Blood Pressure

(End-Stress Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Augusta University

Must not be taking: Nitrates, Glyburide, Cyclosporine, others

Disqualifiers: Cardiovascular, Pulmonary, Renal, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Bosentan can help manage stress-related high blood pressure. Researchers aim to observe the body's response to stress and determine if Bosentan can control blood pressure during stress. Participants will receive either Bosentan or a placebo for three days to compare results. This trial may suit lean or obese adults who identify as Black or White and do not have uncontrolled high blood pressure or major health issues. As an unphased trial, it offers participants the chance to contribute to important research that could lead to better stress management solutions.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that affect blood vessel function, like nitrates, and those that should not be used with bosentan, such as glyburide and cyclosporine.

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

Research has shown that bosentan is safe for use, particularly in treating pulmonary arterial hypertension. Most individuals tolerate it well, though some have experienced liver problems. Regular liver function tests are crucial to detect any issues early. In one study, only 2.8% of participants had increased liver enzymes, indicating that liver side effects are uncommon. Overall, bosentan is considered safe, but monitoring liver health remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for stress-related high blood pressure focus on reducing overall stress or managing symptoms through medications like beta-blockers or ACE inhibitors. However, Bosentan is unique because it acts on endothelin receptors, which play a critical role in blood vessel constriction. By blocking these receptors, Bosentan could potentially reduce blood pressure more directly and effectively than traditional methods. Researchers are excited about Bosentan because it may offer quicker results, potentially showing effects in just a few days, unlike some existing treatments that take longer to work.

What evidence suggests that Bosentan might be an effective treatment for stress-related high blood pressure?

Research has shown that bosentan, which participants in this trial may receive, effectively treats pulmonary arterial hypertension, a type of high blood pressure affecting the lungs. It enables people to be more active with less fatigue. Other studies have found that long-term use of bosentan is safe and stable, allowing for extended use without major issues. Bosentan also appears to improve symptoms and physical endurance in individuals with other types of high blood pressure. The drug blocks endothelin-1, a substance that can tighten blood vessels and raise blood pressure, which may explain its effectiveness for stress-related high blood pressure. ^{2 3 6 7 8}

Who Is on the Research Team?

Ryan Harris, PhD

Principal Investigator

Augusta University

Are You a Good Fit for This Trial?

This trial is for Black and White adults, ages 18-50, who are either lean (BMI < 25) or obese (BMI > 30). It's not for those on low-salt diets, with severe underweight or extreme obesity issues, cardiovascular diseases, pregnant women, uncontrolled high blood pressure patients, or those taking certain medications.

Inclusion Criteria

My body mass index (BMI) is less than 25.

Self-reported Black and White adults

I am considered obese with a BMI over 30.

Exclusion Criteria

You are pregnant.

You are on a diet that limits your salt intake.

I have a heart, lung, kidney, liver, brain, or metabolic condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either placebo or Bosentan for 3 days to evaluate stress response and endothelial function

3 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Bosentan
• Placebo

Trial Overview The study tests how a drug called Bosentan affects blood pressure response to stress compared to a placebo. The goal is to understand the role of endothelin-1 based on previous animal studies by the investigators.

How Is the Trial Designed?

Group I: Bosentan Experimental Treatment 1 Intervention

Sub-Chronic (3 days) Bosentan 250mg/day.

Group II: Placebo Placebo Group 1 Intervention

Stress response and endothelial function will be determined following a three day treatment of placebo

Bosentan is already approved in European Union, United States, Canada, Switzerland, Japan for the following indications:

Approved in European Union as Tracleer for:

• Pulmonary arterial hypertension

Approved in United States as Tracleer for:

• Pulmonary arterial hypertension

Approved in Canada as Tracleer for:

• Pulmonary arterial hypertension

Approved in Switzerland as Tracleer for:

• Pulmonary arterial hypertension

Approved in Japan as Tracleer for:

• Pulmonary arterial hypertension

Who Is Running the Clinical Trial?

Augusta University

Lead Sponsor

Trials

219

Recruited

85,900+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Bosentan is the first oral dual endothelin receptor antagonist approved for treating pulmonary arterial hypertension, significantly improving exercise capacity and symptoms in patients.

Large-scale studies have confirmed bosentan's long-term safety and tolerability, making it a crucial treatment option for pulmonary arterial hypertension and potentially other endothelin-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bosentan: a dual endothelin receptor antagonist. Rubin, LJ., Roux, S.[2019]

Citations

1. withpower.com withpower.com/trial/phase-hypertension-5-2015-4e666

Bosentan for Stress-Related High Blood Pressure · Info ... Bosentan is effective in treating pulmonary arterial hypertension (a type of high blood pressure affecting the lungs) by improving exercise capacity and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1861451/

Long‐term oral bosentan treatment in patients with ... Long‐term bosentan treatment in patients with PAH related to CHD is safe and induces clinical stability and improvement, but the objective exercise values ...

3. clevelandclinicmeded.com clevelandclinicmeded.com/medicalpubs/pharmacy/marapr2002/bosentan.htm

Bosentan (Tracleer™), a New Agent for the Treatment of ... Bosentan represents a new development in the treatment of pulmonary hypertension, a different approach to the pathogenesis of this disease.

4. publications.ersnet.org publications.ersnet.org/content/erj/25/3/502

Bosentan therapy for portopulmonary hypertension After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310±102 m at ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0891584912011380

Bosentan inhibits oxidative and nitrosative stress ... Treatment with the combined ET receptor antagonist bosentan (250 mg/kg/day; day 10 to 21) prevented further increase in RVPSP and RV hypertrophy, decreased ETA/ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2564804/

Long-term effects of bosentan on quality of life, survival ... In most patients, bosentan was associated with improvement or stability of clinical status. The 92% estimate for survival at 48 weeks is a significant ...

7. ecrjournal.com ecrjournal.com/articles/bosentan-pulmonary-arterial-hypertension-associated-congenital-heart-disease-congenital?language_content_entity=en

Bosentan in Pulmonary Arterial Hypertension Associated ... Elevated liver aminotransferase values after bosentan initiation were recorded in 2.8% (IPAH: 8.4%). These data provide additional evidence of the safety of ...

8. go.drugbank.com go.drugbank.com/drugs/DB00559

Bosentan: Uses, Interactions, Mechanism of Action Used in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening.