Vascular Function in Pulmonary Arterial Hypertension
Trial Summary
What is the purpose of this trial?
Many control mechanisms exist which successfully match the supply of blood with the metabolic demand of various tissues under wide-ranging conditions. One primary regulator of vasomotion and thus perfusion to the muscle tissue is the host of chemical factors originating from the vascular endothelium and the muscle tissue, which collectively sets the level of vascular tone. With advancing age and in many disease states, deleterious adaptations in the production and sensitivity of these vasodilator and vasoconstrictor substances may be observed, leading to a reduction in skeletal muscle blood flow and compromised perfusion to the muscle tissue. Adequate perfusion is particularly important during exercise to meet the increased metabolic demand of the exercising tissue, and thus any condition that reduces tissue perfusion may limit the capacity for physical activity. As it is now well established that regular physical activity is a key component in maintaining cardiovascular health with advancing age, there is a clear need for further studies in populations where vascular dysfunction is compromised, with the goal of identifying the mechanisms responsible for the dysfunction and exploring whether these maladaptations may be remediable. Thus, to better understand the etiology of these vascular adaptations in health and disease, the current proposal is designed to study changes in vascular function with advancing age, and also examine peripheral vascular changes in patients suffering from chronic obstructive pulmonary disease (COPD), Sepsis, Pulmonary Hypertension, and cardiovascular disease. While there are clearly a host of vasoactive substances which collectively act to govern vasoconstriction both at rest and during exercise, four specific pathways that may be implicated have been identified in these populations: Angiotensin-II (ANG-II), Endothelin-1 (ET-1), Nitric Oxide (NO), and oxidative stress.
Do I need to stop my current medications to join the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What evidence supports the effectiveness of the drugs used in the clinical trial for pulmonary arterial hypertension?
The research highlights that drugs like endothelin receptor antagonists and phosphodiesterase 5 inhibitors, such as Bosentan and Sildenafil, have shown improvements in exercise capacity and functional class in patients with pulmonary arterial hypertension. These drugs have been effective in increasing the distance patients can walk in six minutes, which is a measure of improved physical function.12345
Is the treatment generally safe for humans?
Research shows that treatments like acetylcholine, vitamin C, and sodium nitroprusside have been studied for their effects on blood flow and vascular function, often showing beneficial effects in managing conditions like hypertension. These treatments have been used in various studies without significant safety concerns, suggesting they are generally safe for human use.16789
How does the drug Selexipag differ from other treatments for pulmonary arterial hypertension?
Selexipag is unique because it is an oral medication that specifically targets the prostacyclin receptor (IP) pathway, which is crucial for dilating blood vessels in the lungs and improving heart function. Unlike other treatments, it is a non-prostanoid, meaning it works differently from traditional prostacyclin-based therapies.1011121314
Research Team
Russell Richardson, Ph.D.
Principal Investigator
George E Wahlen VA Medical Center
Eligibility Criteria
This trial is for healthy young adults (18-30), older adults (65+), and patients with mild to moderate COPD, Group 1 pulmonary arterial hypertension, or Class I-III heart failure. Excluded are those with severe diseases like unstable angina, significant renal disease, severe COPD requiring oxygen, recent heart attacks or surgeries, pregnant women, and anyone at risk from MRI.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants undergo various pharmacologic interventions and exercise tests to assess vascular function and metabolic demand
Follow-up
Participants are monitored for safety and effectiveness after treatment
Open-label extension (optional)
Participants may opt into continuation of treatment long-term to further assess vascular function
Treatment Details
Interventions
- Acetylcholine (Vasodilator)
- Angiotensin-II (Vasoconstrictor)
- BH4 (Antioxidant)
- BQ-123 (Endothelin Receptor Antagonist)
- Fexofenadine (Antihistamine)
- L-NMMA (NOS Inhibitor)
- MitoQ (Mitochondrial Targeted Antioxidant)
- Norepinephrine (Vasoconstrictor)
- Phentolamine (Alpha Adrenergic Receptor Antagonist)
- Ranitidine (H2 Receptor Antagonist)
- Sodium Nitroprusside (Vasodilator)
- Valsartan (Angiotensin Receptor Blocker)
- Vitamin C (Antioxidant)
- Vitamin E (Antioxidant)
- α-Lipoic Acid and L-Ascorbate (Antioxidant)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Russell Richardson
Lead Sponsor