Rare Medical News
Advertisement
Spotlight On
Pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) affects the heart and lungs. It is characterized by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs.
Prevalence
1-9 / 100 000
N/A
US Estimated
N/A
Europe Estimated
Age of Onset
All ages
I27.0
I27.21
Inheritance Pattern
Autosomal dominant
Autosomal recessive
Mitochondrial/Multigenic
X-linked dominant
X-linked recessive
5 Facts you should know
FACT
1
PAH is a progressive and life-threatening condition that leads to right ventricular failure if left untreated.
FACT
2
Women are affected more frequently than men, particularly in idiopathic and heritable PAH.
FACT
3
Early symptoms are often nonspecific, which can delay diagnosis by years.
FACT
4
Genetic mutations, especially in BMPR2, play a key role in disease development in heritable cases.
FACT
5
Targeted therapies have significantly improved survival and quality of life, though PAH remains incurable.
Interest over time
Google searches
Common signs & symptoms
Chest pain
Trouble breathing
Increased pulmonary vascular resistance
Abnormal thrombosis
Fatigue
Elevated right atrial pressure
Current treatments
Riociguat(Brand name: Adempas)
- Manufactured by Bayer HealthCare Pharmaceuticals, Inc.
FDA-approved indication: Treatment of adults with pulmonary arterial hypertension (PAH) WHO Group 1, to improve exercise capacity, WHO functional class and to delay clinical worsening.
Epoprostenol(Brand name: Flolan®)
- Manufactured by Glaxo Wellcome Inc.
FDA-approved indication: Long-term intravenous treatment of primary pulmonary hypertension in NYHA Class III and Class IV patients.
Ambrisentan(Brand name: Letairis®)
- Manufactured by Gilead Colorado
FDA-approved indication: Treatment of pulmonary arterial hypertension (WHO group I) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening
Macitentan(Brand name: Opsumit)
- Manufactured by Actelion Pharmaceuticals Ltd
FDA-approved indication: Treatment of pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). Opsumit also reduced hospitalization for PAH.
References:
Huang WC, Hsu CH, Sung SH, Ho WJ, Chu CY, et al. TSOC pulmonary hypertension committee. 2018 TSOC guideline focused update on diagnosis and treatment of pulmonary arterial hypertension. J Formos Med Assoc. Dec 2019; 118(12):1584-1609. https://pubmed.ncbi.nlm.nih.gov/30926248/Galiè N, Channick RN, Frantz RP, Grünig E, Jing ZC, Moiseeva O, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. Jan 24, 2019; 53(1):1801889. https://pubmed.ncbi.nlm.nih.gov/30545971/Rubin LJ, Hopkins W. The epidemiology and pathogenesis of pulmonary arterial hypertension (Group 1). UpToDate. last updated: Feb 29, 2020; https://www.uptodate.com/contents/the-epidemiology-and-pathogenesis-of-pulmonary-arterial-hypertension-group-1Hopkins W, Rubin LJ. Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy. UpToDate. last updated: Aug 20, 2020; https://www.uptodate.com/contents/treatment-of-pulmonary-arterial-hypertension-group-1-in-adults-pulmonary-hypertension-specific-therapy.
Current treatments
| Title | Description | Phases | Status | Interventions | More Information |
|---|---|---|---|---|---|
| Reducing Right Ventricular Failure in Pulmonary Arterial Hypertension (RELIEVE-PAH) | The objectives of the RELIEVE-PAH study are to obtain first-in-human experience with the study device in patients with severe pulmonary arterial hypertension, including evidence of initial safety, device performance and possible signals of clinical effectiveness. | NA | RECRUITING | DEVICE: V-Wave Interatrial Shunt | More info |
| The MObile Health InterVEntion in Pulmonary Arterial Hypertension (MOVE PAH) Study | Patients with pulmonary arterial hypertension (PAH) have reduced health related quality of life (HRQOL) and impaired exercise capacity. Despite fourteen approved therapies, most patients die within ten years. Increasing physical activity is highly efficacious in PAH, resulting in six-minute walk distance (6MWD) and HRQOL improvement that often exceeds the effect of medications. Prior activity studies required inpatient rehabilitation, which is impractical, hard to sustain, and poorly scalable to a rare disease. The Investigators propose a randomized trial of smart texts versus usual care for 6 months. The Investigators will randomize 100 PAH patients to the mHealth intervention or usual care. The Investigators will test the effect of a text-based mHealth intervention on HRQOL in PAH using the PAH-specific emPHasis-10 questionnaire. The Investigators will also test the effect of an mHealth intervention on exercise capacity, measured by a supervised home-based 6MWD test. Finally, the Investigators will examine the effect of the intervention on time to clinical worsening (composite of PAH therapy escalation, PAH hospitalization, and death) one year after randomization. | NA | RECRUITING | DEVICE: mHealth Intervention|DEVICE: Usual Care | More info |
| Home Rehabilitation Improves Cardiac Effort in Pulmonary Arterial Hypertension | The purpose of this study is to evaluate whether a home rehabilitation program for patients diagnosed with Pulmonary Arterial Hypertension (PAH) will decrease Cardiac Effort (number of heart beats used during 6-minute walk test/walk distance) and improve quality of life. Ultimately, this information could help improve the management of patients with PAH. | NA | RECRUITING | BEHAVIORAL: Exercise|BEHAVIORAL: Standard of Care | More info |
| PAH Exercise Study | Ten patients with PAH who are stable and eligible to initiate sotatercept therapy will participate in a 26 week study that consists of a 24-week intervention period where patients will receive complimentary sotatercept as prescribed, plus a tailored, progressive home exercise program with wrist-worn fitness tracker and oxygen saturation monitoring. | PHASE3 | RECRUITING | OTHER: Home exercise program | More info |
| A Clinical Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (MK-7962-038) | Researchers are looking for more ways to treat PAH. In PAH, the blood vessels in the lungs become thick and narrow, which makes it harder for blood to flow. This causes high blood pressure in the lungs and overworks the heart. PAH can make it hard to breathe and be active. Some standard (usual) treatments for PAH can treat symptoms of PAH but do not stop PAH from getting worse. Sotatercept is a study medicine designed to treat PAH. It is a targeted therapy, which is a treatment that works on certain proteins that play a role in causing PAH. This is a long-term follow-up (LTFU) study. People who took part in certain other studies testing sotatercept for PAH may be able to join this study. The goal of this study is to learn about the long-term safety of sotatercept and if people tolerate it when taken with standard PAH treatment over a longer period of time. | PHASE3 | RECRUITING | BIOLOGICAL: Sotatercept | More info |
| Open-label Extension Study of Seralutinib in Adult Subjects With PAH (PROSERA-EXT) | This open-label extension study will evaluate the long-term safety, tolerability and efficacy of orally inhaled seralutinib in subjects who have completed a previous seralutinib study | PHASE3 | RECRUITING | DRUG: Seralutinib|DEVICE: Gereic Dry Powder Inhaler | More info |
| Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008) | The primary objectives of the study are to evaluate the safety and tolerability, and pharmacokinetics (PK) of sotatercept over 24 weeks of treatment in children ≥1 to \<18 years of age with PAH World Health Organization (WHO) Group 1 on standard of care (SoC). There is no formal hypothesis. | PHASE2 | RECRUITING | DRUG: Sotatercept | More info |
| Right Ventricle Lipid in Pulmonary Arterial Hypertension (PAH) | The investigators propose to study the relationship between right ventricle (RV) steatosis and RV function, exercise capacity, and outcomes in humans with pulmonary arterial hypertension (PAH) and to identify potential drivers of lipid accumulation. | RECRUITING | OTHER: No Intervention | More info | |
| Hormonal, Metabolic, and Signaling Interactions in PAH | Our hypothesis is that optimal treatment of the dysfunctional metabolic pathways which underlie PAH will improve pulmonary vascular function and consequences of the disease. | RECRUITING | More info | ||
| Study of Intravenous ZMA001 in Healthy Subjects | Background: A number of diseases can cause a type of lung injury called pulmonary arterial hypertension (PAH). Most people who develop PAH do not survive more than a few years. A new study drug (ZMA001) may help. ZMA001 is a monoclonal antibody. This type of drug consists of proteins, made in a facility, that are very similar to proteins in a human body. But before giving ZMA001 to people sick with PAH, researchers want to find out how the drug affects healthy people. Objective: To test a drug (ZMA001) in healthy volunteers. Eligibility: Healthy adults aged 18 to 60 years. Design: Participants will be screened. They will have a physical exam with blood tests. They will have a urine test for drug use. They will have a test of their heart function. Participants will come to the clinic for 1 inpatient visit of up to 48 hours. ZMA001 is a liquid administered through a tube attached to a needle inserted into a vein in the arm. Participants will receive this drug only once, during their inpatient stay. Some participants will receive the drug; others will receive a placebo in Cohort 1 only. A placebo is a treatment that looks just like the real drug but contains no medicine. Participants will not know which treatment they are getting in Cohort 1. Cohorts 2-4 will receive a single dose of the study drug, administered through a tube attached to a needle inserted into a vein in the arm. After a screening visit, participants will have 1 inpatient visit and up to 8 outpatient visits over 16 weeks after receiving the treatment. Blood draws and other tests will be repeated. Each outpatient visit is approximately 2 hours long. This study is the first time ZMA001 will be administered to people. | PHASE1 | RECRUITING | OTHER: Placebo Cohort 1 (1.5 mg/kg/dose) only|DRUG: ZMA001 (BC-NKA-20008) | More info |
| PET Image in PAH Patients | Pulmonary arterial hypertension (PAH) is mortal disease affecting the blood vessels of the lung. Despite its morbid prognosis, PAH is often misdiagnosed or ignored, with an average time of 44 months between onset of symptoms to diagnosis and substantial progression of disease severity. Therefore, a pressing need exists to develop non-invasive diagnostic imaging tools, particularly that can detect early disease stages. Efforts have been made to develop such imaging capabilities through platform development of echocardiography, cardiac MRI, chest computed tomography (CT), and positron emission tomography (PET), among others. While some have demonstrated promise, few have shown a precise ability to offer disease quantifications of the diseased lung and vasculature itself, to detect early stages of disease, and to reflect alterations of the lung, vasculature, and right ventricle that reflect the molecular origins of this disease. \[F-18\]FGln has been previously utilized in oncology studies as a non-invasive in vivo imaging biomarker of tumor glutamine flux and metabolism. Our preliminary in vivo pre-clinical rodent studies demonstrated that \[F-18\]FGln demonstrated increased uptake in diseased pulmonary vessels and the right ventricle in a rodent model of PAH. The proposed research study will provide preliminary evidence of the potential to utilize \[F-18\]FGln as a non-invasive imaging biomarker of glutamine flux and metabolism across a range of PAH subjects. | EARLY_PHASE1 | RECRUITING | DIAGNOSTIC_TEST: 18F-FGLN PET Imaging|DRUG: (18F)FPGLU | More info |
| Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH | The purpose of this study is to determine if there is a greater effect to patients with advanced pulmonary arterial hypertension (PAH) by using a combination of two drugs, Treprostinil and Riociquat versus Treprostinil alone | PHASE3 | RECRUITING | DRUG: Treprostinil Injectable Product|DRUG: Riociguat Pill | More info |
| Cardiac Assessment by PV Loop in IPAH and Scleroderma PAH | This observational study is being done to understand why people with scleroderma can develop pulmonary arterial hypertension (high blood pressure in the lungs, abbreviated PAH) and a weak heart muscle (heart failure). The study will also help the investigators understand why people with PAH from an unknown cause (called idiopathic PAH, or IPAH) can also develop a weakened heart muscle. The response of the right side of the heart or right ventricle (RV) to standard PAH therapy in scleroderma-associated PAH and in IPAH will be assessed. Blood and tissue samples will be collected from research participants during participants' normal standard of care procedures. People with scleroderma-associated PAH or idiopathic cause (IPAH) who need a right heart catheterization may join this study. | RECRUITING | More info | ||
| 129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH) | The overall study objectives outlined in this study are to derive 129Xe MRI pulmonary vascular biomarker signatures that differentiate common subtypes of PAH and to determine the ability of 129Xe MRI to longitudinally monitor disease progression and response to therapy in PAH, with the aid of additional assessments, such as labs, echocardiography, and six-minute walk distance (6MWD). | PHASE2 | RECRUITING | DRUG: 129Xe Hyperpolarized | More info |
| A Study of ROC-101 in Patients With Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated With Interstitial Lung Disease (ILD-PH) (ROCSTAR STUDY) | This study evaluates the effect of ROC-101 in adults with either Pulmonary Arterial Hypertension (PAH) or Pulmonary Hypertension Associated with Interstitial Lung Disease (ILD-PH). Each eligible participant will receive standard of care (SOC) plus ROC-101 for a 24-week treatment period, followed by a long-term extension period of the study through the end of the program or marketing approval/authorization. | PHASE2 | RECRUITING | DRUG: ROC-101 | More info |
| A Study to Learn About the Treatment LTP001 in Healthy Participants (Part A) and in Participants With PAH (Part B) | A study to learn about the treatment LTP001 in healthy participants (Part A) and in participants with PAH (Part B) | PHASE1|PHASE2 | RECRUITING | DRUG: LTP|DRUG: Placebo | More info |
| Pediatric Pulmonary Hypertension Network (PPHNet) Informatics Registry | Patients are being asked to be in this research study because medical researchers hope that by gathering information about a large number of children with pulmonary hypertension over time, their understanding of the disease process will increase and lead to better treatment. Investigators believe that pulmonary hypertension in children is different than pulmonary hypertension in adults and this study will help us understand those differences. | RECRUITING | More info | ||
| Rutgers University Study of the Genetics of Pulmonary Hypertension | The goal of this observational study is to learn more about how genes impact the risk of pulmonary hypertension. Anyone 18 or older living in the US is eligible, and a diagnosis of PH is NOT required. Study participation is online, and it takes about 20 minutes to complete health surveys and request a saliva collection kit sent through US mail. In return, study participants may opt to receive information about their genetic ancestry at no cost. | RECRUITING | GENETIC: Saliva sample|OTHER: Health surveys | More info | |
| Sotatercept on Central Cardiopulmonary Performance and Peripheral Oxygen Transport During Exercise in Pulmonary Arterial Hypertension | The purpose of this study is to see if the drug sotatercept given for 36 weeks improves the functioning of the heart and improves quality of life. | PHASE4 | RECRUITING | DRUG: Sotatercept | More info |
| A Study to Learn About the Study Medicine Called PF-07868489 in Healthy Adult People and in People With Pulmonary Arterial Hypertension | The purpose of the study is to learn how the study medicine called PF-07868489 is tolerated and acts in healthy adult people and people with pulmonary arterial hypertension (PAH). Part A: An investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose study to assess the safety, tolerability, and pharmacokinetics (PK) of PF-07868489 in healthy adult participants. Part B: A 24-week, randomized, double blind, placebo-controlled study to assess the safety, tolerability, PK, and pharmacodynamics (PD) of PF-07868489 in adult participants with PAH. | PHASE1|PHASE2 | RECRUITING | DRUG: PF-07868489|DRUG: Placebo for PF-07868489 | More info |
| A Placebo-controlled, Randomized Clinical Trial to Assess the Safety, Feasibility, and Pharmacokinetics of Microbiota Transplant Therapy With Antibiotic Preconditioning and Fiber Supplementation in Patients With Pulmonary Arterial Hypertension | This pilot clinical trial will evaluate the initial safety, feasibility, and pharmacokinetics of microbiota transplant therapy (MTT) with antibiotic pre-conditioning and fiber supplementation vs. placebo in patients with pulmonary arterial hypertension (PAH). This trial will inform development of future trials of MTT as a treatment for PAH. 24 PAH patients will be randomized to receive either MTT with antibiotic preconditioning + fiber supplementation, MTT with antibiotic preconditioning + placebo supplementation, or placebo + placebo supplementation. MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Fiber supplementation will be 10-14 gm oral fiber supplement. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week,12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12. | PHASE1 | RECRUITING | DRUG: MTT with antibiotic preconditioning + fiber supplementation|DRUG: MTT with antibiotic preconditioning + placebo supplementation|OTHER: MTT with placebo + placebo supplementation. | More info |
| Spironolactone for Pulmonary Arterial Hypertension | Background: \- High blood pressure in the lungs, known as pulmonary arterial hypertension (PAH), is a rare disorder. In spite of recent advances in treatment, the death rate remains unacceptably high. Lung blood vessel function can be harmed by progressive injuries, such as inflammation, leading to worsening of the disease. A drug called spironolactone has been known to improve blood vessel function and reduce inflammation. Some people with PAH take spironolactone to help treat fluid retention. However, its effect on inflammation and blood vessel function in patients with PAH is not known. Researchers want to see if spironolactone can help these conditions in people with PAH. Objectives: \- To test the effectiveness of spironolactone in treating pulmonary arterial hypertension. Eligibility: \- Individuals at least 18 years of age with pulmonary arterial hypertension. Design: * This study will last for 24 weeks. Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * Participants will take either spironolactone or a placebo. They will take their study drug or placebo for 7 weeks. Treatment will be monitored with regular blood tests. * In Week 8, participants who have had no reaction to the treatment will receive a higher dose of the drug or placebo. * In Week 12, participants will have a study visit with heart and lung function tests. They will also have a 6-minute walk test, and provide blood and urine samples. * After additional study visits for blood samples, participants will have a final visit in Week 24. The tests from Week 12 will be repeated at this visit. | PHASE2 | RECRUITING | DRUG: Spironolactone|DRUG: Placebo | More info |
| Mobile Health Intervention to Improve Exercise in Pediatric PH | Children and adults with pulmonary arterial hypertension (PAH) have severely reduced daily activity compared to healthy populations. In adults, investigators recently demonstrated that lower baseline daily step counts associated with increased risk of hospitalization and worsening WHO functional class; similarly, reduced step counts associate with hospitalization in children with PAH. This application builds on our recently completed NIH-funded pilot mobile health (mHealth) trial in adult patients with PAH which demonstrated the ability to remotely increase step counts. The investigators now aim to: (1) adapt our mHealth intervention to the developmental needs and interests of adolescents; and, (2) determine if our intervention increases step counts in adolescents, providing the foundation for a larger trial to assess the impact on quality of life and clinical outcomes. | NA | RECRUITING | DEVICE: mHealth Intervention|DEVICE: Usual Care | More info |
| A Study of Pulmonary Hypertension Peripheral Limitations | The investigators are doing this research study to compare whole body aerobic training with isolated leg training (with weights) and its impact on effectiveness in symptoms and quality of life in patients with Pulmonary Arterial Hypertension (PAH). | NA | RECRUITING | BEHAVIORAL: Aerobic Training|BEHAVIORAL: Leg Training | More info |
| Safety and Impact of Low Resistance Exercise Training on Quality of Life in Pulmonary Arterial Hypertension | The purpose of the study is to learn more about how low-resistance training impacts frailty and the quality of life of people with pulmonary arterial hypertension (PAH). Low-resistance training is an evidence-based approach that may help patients improve their functional ability. | NA | RECRUITING | BEHAVIORAL: Low-Resistance Training | More info |
| Xenon MRI Pulm Hypertension | The overall objective outlined in this study is to determine how pulmonary vascular remodeling in PAH at a cellular and pathological level is associated with changes in gas exchange physiology and hemodynamics (monitored with 129Xe MRI/MRS) and how these signals change with disease progression or treatment. | PHASE2 | RECRUITING | DRUG: 129Xe Hyperpolarized | More info |
| Pulmonary Hypertension Association Registry | The PHA Registry (PHAR) is a national study about people who have pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). PHAR collects information from people with PAH and CTEPH who are cared for in participating PHA-accredited Pulmonary Hypertension Care Centers throughout the U.S. PHAR will determine how people with PAH and CTEPH are evaluated, tested, and treated, and will observe how well these participants do. The goal is to see if people with PH are treated according to recommended guidelines, and to see if there are certain factors that can lead to better or worse outcomes. PHAR will include information about people with PAH and CTEPH in the U.S. who are seen at participating PHA-accredited PH Care Centers. PHAR contains data about patient care and outcomes. Specifically, data in the PHAR includes information on diagnosis; clinical status; socioeconomic status; diagnosis test results; body size; treatment information; interest in participating in clinical trials; family health and social history; and information about smoking, alcohol, or drug use. Participants are followed over time, and provide updates such as changes in therapy, how often participants need to go to the hospital, and survival. Such information may help healthcare providers provide better care. | RECRUITING | More info | ||
| Treatment of Pulmonary Arterial Hypertension Using the Aria CV Pulmonary Hypertension System | This prospective study is a multi-center early feasibility study assessing the safety and performance of the Aria CV Pulmonary Hypertension System in patients with pulmonary hypertension and right heart dysfunction. | NA | RECRUITING | DEVICE: Aria CV Pulmonary Hypertension System | More info |
| Pulmonary Hypertension SOLAR | The main goal of this study is to develop a noninvasive signature for pulmonary vascular remodeling in Group 3 PH patients, using hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI). Such a signature may identify Group 3 PH responders to PAH-specific therapies. PAH's unique 129Xe MRI signature has been shown in previous studies. Past studies have lacked a pathologic "ground truth" correlate of these signatures, which could be provided by comparing them with the pathology of lung explant tissue from patients who have undergone a lung transplant. This signature could be validated in a cohort of patients with Group 3 PH in future studies. | PHASE2 | RECRUITING | DRUG: Hyperpolarized 129Xe | More info |
| Natural History Study of Biomarkers in Pulmonary Arterial Hypertension | Background: \- High blood pressure in the lungs, known as pulmonary arterial hypertension (PAH), is a rare disorder. Some people have disease-associated PAH and some have PAH from an unknown cause. Researchers want to follow the natural history of all PAH patients to understand how PAH progresses in order to discover targets for future research into new treatments. To further identify treatment targets, they will compare healthy volunteers to patients with PAH. Objectives: \- To study the natural history of PAH. Eligibility: * Individuals at least 18 years of age who have PAH. * Healthy volunteers at least 18 years of age. Design: * Participants with PAH will have periodic visits to the National Institutes of Health Clinical Center. After the first visit, they will return in 6 months and then yearly or every other year for as long as the study continues. * The first visit will take up to 3 days. It will involve the following tests: * Physical exam and medical history * Blood and urine samples * Heart and lung function tests and imaging studies * Six-minute walk test * Questions about exercise and physical activity * Healthy volunteers will have only one visit to the Clinical Center, during which they will undergo screening tests, and complete many of the same tests as patients with PAH | RECRUITING | More info | ||
| : Vascular Function in Health and Disease | 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. | PHASE1 | RECRUITING | OTHER: Maximum Exercise Tests|DRUG: BH4, L-NMMA, Vitamin C, Vitamin E, α-Lipoic Acid and L-Ascorbate|DRUG: BQ-123|DRUG: Fexofenadine, Ranitidine|OTHER: Angiotensin-II, Valsartan|DRUG: Acetylcholine, Sodium Nitroprusside, Angiotensin-II, Norepinephrine, Phentolamine|DRUG: BQ-123, MitoQ, BH4 | More info |
| Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals | Pulmonary arterial hypertension (PAH) is a severe disease with a delayed diagnosis and markedly elevated mortality. High-risk populations, such as those with known genetic defects, provide a unique opportunity to determine the features of susceptibility and resilience to PAH. This proposal will fundamentally overturn the prevailing understanding of PAH by creating molecularly-driven signatures of susceptibility and resilience, provide novel insight into disease severity, and potentially identify new therapeutic targets. Funding Source - FDA OOPD | RECRUITING | More info | ||
| Study Roles of Heavy Metals and Essential Metal Dyshomeostasis in Pulmonary Arterial Hypertension Patients | Investigators plan to recruit 50 PAH patients from UofL PAH Clinic, with various degrees of severity (25 intermediate risk patients and 20 high risk patients) and 10 age and gender matched controls. PAH patients are evaluated at least every 6 months by the PAH Clinic and blood/urine samples will be obtained at each office visit. Blood, plasma and urine samples will be used to measure 31 metal levels including heavy metals (cadmium, arsenic, cobalt, lead etc.) and essential metals (calcium, copper, iron, zinc, potassium etc.) by the with ICP-MS via the service of ITEMFC. Interactions among the 31 metals in PAH patients, metal concentration differences between intermediate risk PAH, high risk PAH and control groups, the correlation between metal concentrations and the etiology, severity, duration, treatment, and progression of PAH/RV dysfunction over 12 months will be analyzed by CIEHS Biostatistics and Informatics Facility Core. | RECRUITING | DIAGNOSTIC_TEST: Metal level measurements | More info | |
| Repurposing Valsartan May Protect Against Pulmonary Hypertension | This is a Phase 2, single-center, randomized placebo controlled trial of valsartan (an angiotensin receptor blocker) in adults with pulmonary arterial hypertension. The study will evaluate the safety and clinical efficacy of a 24-week course of valsartan. | PHASE2 | RECRUITING | DRUG: Valsartan 40 mg|DRUG: Placebo | More info |
| Pulmonary Hypertension Biorepository and Registry | Establish a pulmonary hypertension registry and biorepository to lead towards a further understanding of the disease. | RECRUITING | More info |