Klippel-Trenaunay Syndrome

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.

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.

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.

This research aims to evaluate the safety and effectiveness of different light doses in treating adults aged 18 to 75 with Port-Wine Birthmarks PWB. The study is a multi-center, randomized, double-blind, vehicle-controlled Phase 2 trial conducted in two sequential stages. It focuses on comparing Hemoporfin photodynamic therapy PDT with a vehicle placebo control using fixed drug dosing and varying light fluences. Participants will be randomly assigned to receive either Hemoporfin PDT or vehicle PDT via intravenous infusion at a fixed dose of 5 mgkg. They will undergo fixed laser irradiation for a set time in cycles lasting 8 weeks. Each participant may receive up to three treatment cycles. The study consists of a Screening Period, Treatment Period, efficacy evaluation for subsequent treatment, and an End of Study phase, lasting up to approximately 44 weeks. Throughout the study, participants will be closely monitored for local and systemic adverse events. Researchers will assess changes in PWB severity using the Port Wine Birthmark-Investigator Global Assessment PWB-IGA scale and other measures from baseline until the studys end. Regular evaluations include physical exams, safety assessments, and efficacy reviews, ensuring participant health and adherence over the entire study duration.

Researchers are conducting a phase 3, double-blind, randomized, placebo-controlled study to evaluate the effectiveness and safety of KP-001 in patients aged 2 years and older with common venous malformations, common lymphatic malformations, or Klippel-TrenaunayCLOVES syndrome. This adaptive, multicenter trial will take place across sites in North America, Canada, Taiwan, and South Korea and includes oversight by an independent data monitoring committee that may adjust the study based on interim results. Participants will undergo a screening period up to 42 days before treatment begins. During the first 24 weeks, patients will receive either KP-001 oral daily doses 100 mg or lower based on body weight or placebo in a double-blind manner. After 24 weeks, all participants will enter an open-label extension phase where everyone receives KP-001 until 52 weeks. A follow-up visit is scheduled 30 days after the last dose, and patients who discontinue treatment are encouraged to continue study assessments. Throughout the study, vital signs and safety labs including blood counts, chemistry, coagulation tests, and urinalysis will be regularly monitored. Exploratory assessments will examine symptom changes using patient-reported scales such as the Numeric Rating Scale NRS for pain and Patient Global Impression scores. The primary measure is the change in volume of target lesions by MRI at 24 weeks. Secondary outcomes include symptom changes, lesion volume at other time points, clinical event monitoring, and adverse event tracking up to 52 weeks post-dose. Participants will be closely observed for safety and treatment effects during the entire study period.

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.

Researchers are evaluating the effects of alpelisib film-coated tablets compared to placebo in participants with lymphatic malformations LyM caused by a PIK3CA mutation. This phase IIIII study aims to assess changes in radiological response and symptom severity during treatment. The study includes both pediatric and adult participants and is conducted in multiple centers with a two-stage design. The study has two main stages. Stage 1 is a 24-week open-label phase where adult 18 years and older and pediatric 6 to 17 years participants receive different doses of alpelisib to determine the best doses for Stage 2. Stage 2 is a 24-week randomized, double-blind, placebo-controlled phase to confirm the efficacy and safety of the selected doses in both adults and children aged 6 to 17, followed by an open-label extension. Additionally, Stage 2 includes an open-label core phase for pediatric participants aged 0 to 5 years receiving alpelisib. Participants undergo screening to confirm eligibility, including confirmation of a PIK3CA mutation and measurable lesions. Throughout the study, participants will have radiological assessments, symptom evaluations using patient global impression scales, and monitoring of safety and pharmacokinetics. The study includes regular reviews by an independent committee to ensure safety. The total study duration includes a 24-week core treatment phase and potential extensions for long-term monitoring, lasting up to several years.

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.

Researchers are conducting the Comprehensive HHT Outcomes Registry of the United States CHORUS, an observational study focusing on Hereditary Hemorrhagic Telangiectasia HHT, a rare genetic condition causing abnormal blood vessels in various organs. The study aims to better understand HHT, its symptoms, complications, and how it affects peoples lives. By collecting detailed information over time, the study hopes to improve knowledge of the disease and assist in developing new treatments. Participants diagnosed with HHT based on specific criteria or genetic testing will be included in the registry. The study will collect long-term data both retrospectively and prospectively from about 10,000 patients across multiple centers in the U.S. Over up to 10 years, participants will provide information through medical records and yearly questionnaires, helping researchers track changes in health, treatments, and symptoms. During participation, individuals will allow access to their medical records and answer study questions at enrollment and annually for up to 10 years or until the study ends. The data collected includes demographic details, diagnosis, family history, test results, symptoms, and treatments. The main outcomes measured over 10 years include baseline health status and clinical outcomes using specific assessment scales. The study also monitors severity of nosebleeds, development of vascular malformations, treatment results, and serious health events related to HHT.

This research aims to evaluate the effectiveness and safety of a more stable polycinnamyl alcohol foam compared to ordinary foam in treating venous malformations of the head and neck. Venous malformations are abnormal blood vessel formations, and foam sclerotherapy has become a widely used method for treatment. This trial is designed as a prospective, randomized clinical study to provide clearer evidence and better treatment options for these malformations. The study compares two types of foam treatments produced by mixing a 1% polycinnamyl alcohol solution with air using Tessaris method. One foam type includes 0.05% hyaluronic acid, making it more stable with a longer half-life than the ordinary foam. Treatments are injected into the venous malformations to displace blood and maintain contact with vessel walls, potentially enhancing therapeutic effects. The trial assesses whether this increased stability improves treatment outcomes and safety. Participants aged 14 to 60 years with diagnosed head and neck venous malformations will receive foam injections and be monitored over 3 to 4 weeks after treatment. Researchers will measure the remission rate, lesion volume, and number of injections needed. Safety and efficacy evaluations will be conducted during follow-up visits, with treatment repeated as necessary based on condition. The studys total duration extends until June 2026, ensuring thorough assessment of treatment results and participant well-being.