NCT02966665 · Russell Richardson
: Vascular Function in Health and Disease
What this study is about
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.
View original scientific description
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.
Interventions
OTHER
Maximum Exercise Tests
Graded exercise test to volitional exhaustion (stationary bike or treadmill), maximal handgrip test, maximal leg extension test, and maximal plantar flexion test.
DRUG
BH4, L-NMMA, Vitamin C, Vitamin E, α-Lipoic Acid and L-Ascorbate
Catheter placement in femoral artery and femoral vein; resting measurements of blood pressure, heart rate and blood flow; flow mediated vasodilation test, passive leg movement test, exercise bouts, electromyography and exercise training regimen at baseline and following treatment with Nitric Oxide blockade via infusion of N-monomethyl-L-arginine (L-NMMA) (0.4 mg/kg/min), antioxidant cocktail (Vitamin C, Vitamin E, alpha-lipoic acid) ingestion, L-ascorbate injection, BH4 ingestion.
DRUG
BQ-123
Catheter placement in femoral artery and femoral vein; resting measurements of blood pressure, heart rate and blood flow; flow mediated vasodilation test and exercise bouts at baseline and following treatment with endothelin-1 receptor antagonist BQ-123 (D-tryptamine-D-aspartic acid-L-proline-D-valine-L-leucine).
DRUG
Fexofenadine, Ranitidine
Catheter placement in femoral artery and femoral vein; resting measurements of blood pressure, heart rate and blood flow; flow mediated vasodilation test and exercise bouts at baseline and following treatment with Histamine H1 receptor antagonist fexofenadine (Allegra) and Histamine H2 receptor antagonist ranitidine (Zantac).
OTHER
Angiotensin-II, Valsartan
Catheter placement in femoral artery and femoral vein; resting measurements of blood pressure, heart rate and blood flow; flow mediated vasodilation test, muscle sympathetic nerve activity measurement, and exercise bouts at baseline and following treatment with Angiotensin-II receptor agonist (angiotensin-II) and antagonist Valsartan (Diovan).
DRUG
Acetylcholine, Sodium Nitroprusside, Angiotensin-II, Norepinephrine, Phentolamine
Catheter placement in femoral artery and femoral vein; resting measurements of blood pressure, heart rate and blood flow; flow mediated vasodilation test, muscle sympathetic nerve activity measurement; vasodilation with nitroglycerin followed by Angiotensin-II and Alpha Adrenergic blockade with infusions of Acetylcholine, Sodium Nitroprusside, Angiotensin-II, Norepinephrine and Phentolamine (Regitine).
DRUG
BQ-123, MitoQ, BH4
Catheter placement in femoral artery and femoral vein and muscle biopsy; Nuclear Magnetic Resonance (NMR) scanning and exercise bouts at baseline and following treatment with BQ-123 with or without oral mitochondria-targeted antioxidant (MitoQ) or oral BH4.
Primary outcome measures
Change in Limb Blood Flow
Time frame: Baseline and 1 hour
Change in local limb blood flow as measured by ultrasound Doppler in units of milliliters per minute (mL/min) from baseline to up to 1 hour following study interventions
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Healthy Young Volunteers: 18-30 years of age with no diseases or conditions that would affect their participation in the study
- Healthy Older Controls: volunteers 65 years of age or older with no diseases or conditions that would affect their participation in the study
- Coronary Angiography subjects: patients undergoing routine coronary angiography
- Chronic Obstructive Pulmonary Disease subjects: patients diagnosed with mild to moderate COPD
- Pulmonary Arterial Hypertension subjects: patients with idiopathic or heritable Group 1 pulmonary arterial hypertension
- Heart Failure subjects: patients with Class I, II or III New York Heart Association symptoms of Heart Failure
- Hypertension subjects: patients diagnosed with chronic high blood pressure
Exclusion criteria
- Severe COPD (use of supplemental oxygen, or have a one-second forced expiratory volume of less than 30% predicted)
- History of myocardial infarction
- History of percutaneous coronary revascularization
- History of coronary artery bypass grafting
- Unstable angina pectoris
- History of variant angina
- Ejection fraction \< 50%
- Significant renal disease (Glomerular Filtration Rate \< 50 mL/min/1.73m2)
- Subjects whose medical care or safety may be at risk from undergoing a Magnetic Resonance Imaging examination (e.g. pacemaker, metal implants, certain types of heart valves)
- Subject is pregnant
- Subject has physical ailments (other than COPD, PAH, HF, or hypertension) that would prevent them from study participation in the judgment of the investigator
Where
- Salt Lake City, Utah
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 26, 2025 · Source of record for eligibility and locations