Abnormal Vascular Flow (Arteriovenous Malformation)

Researchers are evaluating a new 10-minute cardiovascular magnetic resonance CMR imaging protocol designed to improve current CMR procedures for patients with various heart conditions, including coronary artery disease, cardiomyopathies, and other cardiac diseases. The study aims to develop a standardized, contrast-free imaging method that can be applied to about 70% of cardiac patients. The goal is to assess whether this shorter protocol enhances diagnostic decision-making and reduces healthcare costs. The study involves two groups healthy volunteers over 18 years old without significant cardiovascular or respiratory conditions, and patients over 18 years who require a clinically indicated CMR exam. The new protocol focuses on heart function and tissue characterization without using contrast agents. Researchers will compare the new 10-minute protocol to standard CMR imaging, evaluating its clinical feasibility, performance, and cost-effectiveness in different patient populations. Participants will undergo CMR scans using both the new and standard protocols. Researchers will monitor diagnostic results, scan completion rates, scan sequence times, adverse events, and cost differences between methods. Various heart tissue measurements and reproducibility between different readers and scanners will also be assessed. The study spans from 2019 to 2025, with ongoing safety monitoring during imaging sequences and a focus on improving the efficiency and quality of cardiac imaging.

This research aims to understand how menopause affects the risk of cardiovascular diseases such as atherosclerosis, heart attacks, and strokes in women. It focuses on the time around menopause when estrogen production stops, which is linked to a higher risk of these conditions. The study will follow 200 women from before menopause to at least 10 years after, using advanced methods to observe changes in blood vessels, the heart, and the brain, along with microRNA analysis of blood and tissue samples. Participants will be observed over a long period with repeated assessments before menopause and at 1, 3, 5, 10, and 20 years after menopause. These assessments include invasive and non-invasive measures of vascular function, as well as monitoring changes in skeletal muscle proteins and RNA expression from muscle and blood samples. Blood pressure will also be tracked regularly during this time. Women involved in the study will undergo detailed cardiovascular and biological evaluations at various time points throughout the study. This includes tests of blood vessel function, muscle tissue analysis, and blood sample collections. The researchers will also monitor blood pressure and other health indicators to understand the long-term impact of menopause on cardiovascular health. The total participation may last over 20 years, providing extensive data on how menopause influences disease risk over time.

Researchers are evaluating the safety and effectiveness of RLY-2608, a mutant-selective oral PI3K inhibitor, in adults and children with PIK3CA Related Overgrowth Spectrum PROS and malformations driven by PIK3CA mutation. This Phase 2 study has three parts Part 1 focuses on dose selection, Part 2 includes exploratory single-arm cohorts for different participant groups, and Part 3 is a randomized, double-blinded study comparing RLY-2608 to a placebo. Participants receive RLY-2608 orally in various doses depending on their age group and study part. Children aged 2 to under 6 years and 6 to under 12 years undergo dose escalation to find the recommended dose, while older participants receive established doses. Part 3 involves randomization to either RLY-2608 or placebo for participants aged 6 years and older. Each part includes dosing cycles and treatment schedules designed to assess safety and efficacy. During the study, participants undergo assessments including lesion volume measurements, blood tests, ECGs, and biopsies to confirm PIK3CA mutation status. Researchers monitor adverse events and treatment effects through regular visits and imaging at baseline, Week 12, and Week 24. Patient-reported outcomes and quality of life measures are also collected monthly in Part 3. The study spans several years, with ongoing safety and efficacy evaluations throughout treatment and follow-up periods.

Researchers are evaluating non-invasive imaging methods to assess skin blood flow dynamics. This study aims to test and validate how well these imaging technologies perform by using a pressure cuff to create changes in blood flow, ranging from low flow ischemic to high flow hyperemic. The focus is on establishing the basic feasibility of these imaging tools in detecting vascular changes. The study uses Multi-Spectral Imaging and Laser Speckle Imaging, both non-contact optical devices. Multi-Spectral Imaging measures concentrations of total, deoxygenated, and oxygenated hemoglobin in tissue, while Laser Speckle Imaging measures relative blood flow at different times. A pressure cuff occlusion is applied to stimulate changes in blood flow for these devices to detect. Participants will be observed using these imaging methods during vascular occlusion procedures. The main outcome measured is skin blood flow over a 4-week period. The study includes healthy volunteers aged 18 and older and involves non-invasive tests without treatment. Researchers will monitor blood flow changes and the performance of the imaging devices during the study period, which began in 2011 and is expected to continue until 2028.

This research aims to explore the potential use of enalapril to treat painful venous malformations, which are congenital vascular defects that can cause disfigurement and pain, affecting patients quality of life. The study investigates whether enalapril can reduce the pain and volume of these malformations and improve quality of life in affected patients aged 18 to 70. The trial is a phase 2, single-center, single-arm pilot study led by Oslo University Hospital.

Researchers are investigating targeted drug therapies for patients with vascular malformations that are resistant to standard treatments or for whom standard treatments are unsuitable. These vascular malformations are classified as either slow-flow or fast-flow types, driven by genetic changes in two specific signalling pathways. This phase II open-label trial aims to evaluate the effects of 48 weeks of treatment using either alpelisib for slow-flow vascular malformations with PI3K pathway mutations or mirdametinib for fast-flow vascular malformations with MAPK pathway mutations. Participants are divided into two treatment groups based on their vascular malformation type and genetic mutation. Those with slow-flow malformations and PI3K pathway mutations will receive alpelisib, an oral PI3-kinase inhibitor, for 48 weeks followed by a 24-week follow-up. Those with fast-flow malformations and MAPK pathway mutations will receive mirdametinib, an investigational oral MEK inhibitor, also for 48 weeks followed by 24 weeks of follow-up. Both treatments are given as monotherapy and involve genetic testing before enrollment to confirm mutations. Throughout the study, participants will undergo various assessments including symptom evaluations using the Vascular Malformation Patient Specific Outcome Measure VM-PSOM and OVAMA questionnaires, MRI scans to measure lesion size, and monitoring for adverse events. The primary outcome is the improvement in the most significant symptom after 48 weeks of treatment. Follow-up visits continue for 24 weeks after treatment ends to monitor ongoing effects and safety. The total participation duration for each patient is approximately 72 weeks.

Heart disease is the leading cause of death worldwide, contributing to 16% of global fatalities and imposing a significant economic burden, especially as the population ages. Some patients with heart disease experience symptoms not relieved by medications and require coronary artery bypass graft CABG surgery. Although CABG can improve chest pain and has life-prolonging potential, it may increase inflammation and is often accompanied by high levels of anxiety and depression around the time of surgery, which can affect health outcomes and quality of life. This trial is a randomized controlled feasibility study comparing a brief, two-session telehealth Acceptance and Commitment Therapy ACT intervention to treatment as usual for patients undergoing CABG surgery. The ACT intervention focuses on psychological flexibility through core processes such as being present, opening up, and doing what matters, and includes workbooks and mindfulness audio exercises. The control group receives usual preoperative care, including appointments with surgeons and nurse practitioners and educational workbooks about hospital orientation and lifestyle factors. Participants will be assessed on measures of anxiety, depression, psychological flexibility, well-being, cardiovascular health-related quality of life, and inflammation markers before surgery and at 8 weeks after. Researchers will monitor feasibility factors like participant satisfaction, adherence, enrollment, intervention delivery, and retention. The study aims to evaluate both the feasibility and preliminary effects of ACT during the perioperative period for CABG patients, helping guide future larger trials.

Researchers are evaluating the efficacy and safety of FCN-159, an oral investigational MEK inhibitor, in patients with brain arteriovenous malformations BAVM who are not suitable for surgery, radiotherapy, or embolization. This open-label Phase 2 study aims to address the lack of available drug treatments for BAVM by comparing FCN-159 with a no-treatment control group. The study will recruit 10 participants, stratified by gender, age, lesion site, and Spetzler-Martin grade, who have no prior rupture of the malformation. Participants in the treatment group will receive 8 mg of FCN-159 orally once daily in continuous 28-day cycles until disease progression, unacceptable side effects, or other end-of-treatment criteria are met. The control group will be observed without treatment during the study period. Radiological evaluations using Silence-MRA will occur at 3, 6, and 12 treatment cycles after starting therapy, then every 6 cycles and at the end of treatment to assess response. During the study, participants will undergo various assessments including imaging scans such as Silence-MRA and DSA, MRI evaluations of lesion volume and blood flow, and monitoring for events like intracranial hemorrhage and epilepsy. Safety and adverse events will be tracked throughout the 12-month period to measure overall response rate and other health outcomes. Participants must complete follow-up visits and meet specific health criteria to ensure safety and data quality.

Researchers are evaluating the safety and effectiveness of everolimus monotherapy in adults with vascular malformations. This single-arm exploratory trial is conducted by Xuanwu Hospital, Capital Medical University, and includes adult patients aged 18 to 65 who have vascular malformations confirmed by MRI and are unsuitable for effective surgical treatment. Participants will take oral everolimus 10 mg daily in continuous 28-day treatment cycles. Treatment will continue until disease progression, intolerable side effects, lack of benefit as judged by the investigator, study end, or other criteria for stopping treatment. The study includes assessments at multiple points, including after 3, 6, and 12 treatment cycles, and every 6 cycles thereafter. During the study, participants will undergo MRI scans to measure lesion volume and assess microbleeding, iron deposits, and hemorrhage risk. Clinical signs, symptom scores, and quality of life will also be evaluated. These evaluations are scheduled during screening, after certain treatment cycles, and at the end of treatment. The main outcome measured is the response rate based on MRI after one year of treatment.

Cerebral arteriovenous malformations AVMs are tangled abnormal blood vessels called nidus that directly connect arteries to veins, bypassing normal circulation. These malformations are a significant cause of hemorrhagic stroke. Researchers are studying whether bleeding from cerebral AVMs is linked to small vessels near the nidus, possibly involving white blood cells and platelet-related microvascular issues. This observational study examines the relationship between blood biomarkers and the risk of bleeding in cerebral AVMs. Participants include patients with cerebral AVMs who are undergoing treatment such as surgery or endovascular methods, or who are being clinically monitored without intervention. The study measures markers related to blood vessel lining, platelets, neutrophils, and new blood vessel growth at six months to understand their connection to bleeding risk. Participants will provide blood samples that researchers analyze for specific biomarkers related to AVM prognosis. The main outcomes focus on associations between these blood markers and bleeding risk over six months. The study involves monitoring health status and collecting data without administering treatments, with participation length depending on individual follow-up schedules.