Clinical Research Directory

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.

Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension

The purpose of this study is to demonstrate superiority of macitentan 75 milligrams (mg) in prolonging the time to the first clinical events committee (CEC)-adjudicated morbidity or mortality (M/M) event in participants with symptomatic pulmonary arterial hypertension (PAH) compared to macitentan 10 mg.

Fibrotic Disease Activity in Cardiopulmonary Disorders Using 18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74) PET/CT Imaging

Background: Injury or diseases of the heart and lung can sometimes cause scar tissue (fibrosis) to build up in those organs. Current imaging scans can see this scar tissue once it has formed, but researchers want to find a way to detect the fibrosis in its earliest stages, while there might still be time to prevent serious damage. A new tracer (a radioactive substance injected during imaging scans) may be able to help. Objective: To test a new tracer (18F-FAPI-74) during imaging scans in people with heart or lung disease. Eligibility: People aged 18 years and older with lung or heart disease that may cause scarring in those organs. Design: Participants will have 6 clinic visits over 2 years. Participants will be screened: They will have blood tests and tests of their heart and lung function. Those with heart disease will have a magnetic resonance imaging (MRI) scan of the heart. The study tracer will be used with positron emission tomography (PET)/computed tomography (CT) scans. The study tracer will be injected into a vein in the arm. Participants will lie on a padded bed that slides through a donut-shaped machine. Participants will have scans with the study tracer 2 times, 8 to 12 months apart. They will also have standard CT scans and blood tests during these visits. They will also have blood tests at 3 and 6 months between these visits. Participants will have a follow-up visit after 18 to 24 months. The study scans, MRI and standard CT scans, and lung function tests may be repeated....

A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension

The purpose of this study to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, that leads to similar exposure as adults doses in children from greater than or equal to (\>=) 2 to less than (˂) 18 years of age with Pulmonary Arterial Hypertension (PAH), by investigating the PK of selexipag and its active metabolite ACT-333679 in this population.

Safety and Efficacy of Continued CS1 Treatment of Patients With Pulmonary Arterial Hypertension

CS1-004 will be an extension of the CS1-003 Study. The primary objective of the CS1-004 study is to evaluate long-term safety and tolerability of continued treatment with CS1.

Understanding the Effects of Pulmonary Arterial Hypertension on Lean Muscle Mass-Substudy

After completion of the Baseline study visit for the main study (MUSCLE UP-PH), participants at the University of Pennsylvania location will be invited to participate in an optional substudy. The substudy will implement a low-load resistance exercise training for the lower extremities, focusing primarily on the gastrocnemius muscles. The goal of this intervention is to understand how low-load resistance training will impact blood flow and oxygen tissue extraction on the lower legs.

Exercise-based Rehabilitation in Patients With Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare and severe disease characterized by elevation of pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR) due to the narrowing of small pulmonary arteries. The European Society of Cardiology (ESC) and the European Respiratory Society (ERS) recommend supervised exercise-based rehabilitation as part of the treatment of PAH patients alongside optimal medical therapy (Level of evidence A, Class of recommendation I). Studies on exercise-based rehabilitation for PAH patients are limited, and most interventions have been conducted at least partially in hospital settings. Unlike more common cardiovascular diseases, there are no detailed international exercise guidelines tailored specifically for PAH patients. This study aims to verify that a group-based outpatient rehabilitation protocol suitable for the Finnish healthcare system improves exercise capacity, quality of life, and physical activity of PAH patients and is safe for appropriately selected patients. Additionally, the study aims to determine whether PAH patients adhere to regular exercise training and whether physical activity increases in the long term. The goal is to assess whether an outpatient rehabilitation protocol, designed for the Finnish healthcare system, can achieve similar results to those observed in previous international studies. The primary outcome measure is the change in the six-minute walking distance (6MWD) compared to the patient's baseline. Long-term 6MWD data are often available for patients. The 6MWD is the most commonly used primary outcome in randomized and controlled PAH drug trials, and improvements in this test have been the basis for drug approvals. An improvement of 33 meters in the 6MWD is considered clinically significant, and the goal is to achieve this change with group-based outpatient rehabilitation. Secondary outcomes include changes in quality of life (SF-36), WHO functional class, NT-proBNP levels, echocardiographic parameters, ESC/ERS risk-stratification score (four-strata model), muscle strength, respiratory measures, balance, daily step count, and insomnia severity.

Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)

The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.

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.

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.

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.

An Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) for Pulmonary Arterial Hypertension (PAH)

The primary purpose of the study is to evaluate the safety and tolerability of the long-term use of TPIP in participants with PAH from studies INS1009-201 (NCT04791514), INS1009-202 (NCT05147805) and other lead-in studies of TPIP in participants with PAH.

A Study to Evaluate the Efficacy and Safety of Once Daily Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Arterial Hypertension (PAH)

The primary objective of this study is to evaluate the effect of 24-weeks of once daily treatment with TPIP compared with placebo on exercise capacity in adults with PAH.

A Study of HS235 for Treatment of Pulmonary Arterial Hypertension (PAH) in Adults

Phase 1b/2 Study of HS235 Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of the Activin Signaling Inhibitor HS235 Added to Background Treatment in Adults with Pulmonary Arterial Hypertension (PAH)

Empagliflozin to Improve Right Ventricular Function in Pulmonary Arterial Hypertension

Randomized, triple-masked, parallel arm clinical trial of empagliflozin versus placebo in pulmonary arterial hypertension (PAH) participants on stable approved PAH-targeted medical therapy.

CS1 Added to Standard of Care Therapy for Pulmonary Arterial Hypertension

This Phase 2 study (EPIMODE) will evaluate the efficacy and safety of CS1 compared with placebo when added to standard-of-care therapy in participants with pulmonary arterial hypertension. Participants completing Treatment Period 1 (Week 36) will be re-randomized to continue or switch study treatment for Treatment Period 2 through Week 52.

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.

Pulmonary Hypertension: Intensification and Personalisation of Combination Rx

The goal of this clinical trial is to evaluate the capacity of implantable/remote technology for early evaluation of drug therapies in patients with pulmonary arterial hypertension (PAH). The main question it aims to answer is whether structured changes in clinical therapy will be detectable using implanted regulatory approved devices. Participants will will be implanted with approved medical devices and will enter into a study of approved drugs to assess physiology, activity and patient reported quality-of-life (QoL) outcomes. Researchers will compare two therapeutic strategies in each individual patient to see if the study design provides enough evidence to personalise drug treatment plans.

A Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (PAH) in India (MK-7962-037)

Researchers are looking for other ways to treat people in India with pulmonary arterial hypertension (PAH), also known as Group 1 pulmonary hypertension (PH). In PAH, the blood vessels in the lungs become thick and narrow, which makes it harder for blood to flow to the lungs. This causes high blood pressure in the lungs and can overwork the heart. PAH can make it hard to breathe and be active. Researchers want to learn if sotatercept, the study medicine, can be given with standard treatment to help treat PAH. The standard treatment (the usual treatment) for PAH includes one or multiple medicines. However, these may not fully work or treat the symptoms of PAH in some people. The goal of this study is to learn about the safety and tolerability of sotatercept when it is given with standard treatment to people in India.

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.

DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia

This is a Phase 1/2, randomized, double-blind, placebo-controlled, first-in-human study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of subcutaneously administered DIAG723 in adult patients with hereditary hemorrhagic telangiectasia (HHT). The study consists of three parts: Part A (dose escalation): Single ascending subcutaneous doses of DIAG723 are evaluated in sequential cohorts to assess safety, tolerability, and pharmacokinetics. Part B (dose expansion): Multiple doses of DIAG723 administered over 13 weeks are evaluated in patients with HHT to assess safety and preliminary efficacy. Part C (dose expansion): Multiple doses of DIAG723 administered over 13 weeks are evaluated in patients with HHT and concomitant pulmonary arterial hypertension to assess safety and exploratory clinical effects in this population. Participants will be randomized within each study part to receive DIAG723 or placebo. The study includes dose escalation in Part A and dose expansion in Parts B and C.

A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)

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.

Myocardial Metabolic Flux in Pulmonary Arterial Hypertension

The rationale for this study is that GLP-1 agonist treatment is likely to influence myocardial substrate utilisation, changing the predominant source of metabolic energy within the heart to a more energetically efficient form. This is represented by a surrogate for improved mitochondrial efficiency with reduction in myocardial lactate levels (produced by inefficient myocardial glycolysis, prevalent in the ventricles of patients with pulmonary hypertension), which can be measured by 31P-magnetic resonance spectroscopy (31P-MRS).

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