Sheffield

Researchers are evaluating two different pacing methods for patients with slow heart rates in this multi-center trial. The study compares the standard right ventricular pacing with a newer physiological pacing approach, which includes His bundle pacing or left bundle pacing. This trial aims to better understand the effects of these pacing methods on heart function and patient outcomes over time, including a sub-study focused on heart muscle changes related to pacing. Participants will receive a pacemaker implanted at a participating center and be randomly assigned to either right ventricular pacing or physiological pacing. For physiological pacing, if His or left bundle pacing is not successful, biventricular pacing will be used instead. The trial includes an optional echocardiographic sub-study for some patients to assess heart changes over 24 months. Participants will be followed for up to 78 months, with assessments at baseline and every six months. Researchers will measure outcomes such as survival, heart failure events, quality of life questionnaires, symptoms, device-related safety events, and heart rhythm data collected from the pacemakers. The sub-study will use echocardiograms to evaluate changes in heart volume and pumping efficiency. This comprehensive follow-up aims to capture both clinical effects and mechanistic insights of the pacing methods.

This research focuses on pregnant women whose unborn babies have been diagnosed with Congenital Diaphragmatic Hernia CDH, a condition where a hole in the diaphragm allows organs to move into the chest. The study aims to use images taken during routine medical care to create 3D animations and models of the baby and the CDH. These models help parents understand the condition and assist surgeons in planning surgery after birth. The study involves using existing routine scans from pregnant women referred for fetal MRI without any additional intervention. Researchers will create detailed 3D visualizations from these images to better illustrate the size of the diaphragmatic hole and the position of the organs. The study includes patients from diagnosis through to the post-operative period after birth. Participants will be pregnant women attending a fetal medicine unit who have agreed to take part. Researchers will collect baseline information such as patient demographics. The study observes the use of 3D imaging to support clinical management and surgical planning. Participation involves no additional treatment, only the use of images already taken during standard prenatal care. The study is ongoing and will continue until June 2025.

Researchers are working to create and use a comprehensive database focused on intracranial aneurysms IA. This project collects and studies clinical history, imaging data, biological samples, and other information to understand factors linked to the formation and rupture of aneurysms. They aim to identify genetic, environmental, and anatomical markers, as well as evaluate outcomes from different treatment strategies and improve patient care protocols. Participants include patients with diagnosed aneurysms, both ruptured and unruptured, family members of affected individuals, and healthy volunteers. Data collected involves detailed clinical records, imaging scans like MRI angiography and CT angiography, and various biological samples such as blood, cerebrospinal fluid, saliva, and stool. Consent covers access to medical records, use of biological samples, and potential future research uses including genetic analyses. During the study, participants provide health and lifestyle information, imaging data, and biological samples. Researchers will monitor multiple long-term outcomes including disease progression, life expectancy, quality of life, neurological and cognitive status, and treatment effects over periods up to 20 years. Data confidentiality is maintained, and participants can withdraw at any time without affecting their medical care. The study aims to validate disease models and support advances in aneurysm management and research.

Researchers are investigating new treatments for Pulmonary Arterial Hypertension PAH, a condition where the blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and making it difficult for the heart to work properly. PAH can lead to breathing difficulties and reduced activity levels. While current treatments help manage symptoms, they do not stop the disease from progressing. Sotatercept is a study medicine designed to target specific proteins involved in PAH, and this long-term follow-up study aims to assess its safety and tolerability when used alongside standard PAH treatments over an extended period. Participants who have completed previous sotatercept PAH studies may join this open-label follow-up study. Those from blinded studies will start sotatercept at 0.3 mgkg by subcutaneous injection every three weeks and may increase to 0.7 mgkg. Participants from unblinded studies will continue their current dose and may also increase to 0.7 mgkg. The study focuses on monitoring sotatercept use combined with background PAH therapy to observe long-term effects. Throughout the study, participants will undergo regular assessments including tracking adverse events, laboratory tests for blood and chemistry markers, body weight, blood pressure, and electrocardiograms up to approximately 7 years. Additional measurements include walking distance tests, heart function markers, and risk scores related to PAH. Safety monitoring and tolerance to the medication will be closely observed over time to better understand sotatercepts long-term impact in managing PAH.

Researchers are evaluating how different doses of galvokimig compare with a placebo in adults with moderate-to-severe atopic dermatitis, a chronic skin condition. This Phase 2 study aims to understand the relationship between the dose given and its effects on the condition, focusing on safety, how the drug moves through and acts in the body, and its overall impact on the disease. Participants will be randomly assigned to receive one of three different doses of galvokimig or a placebo during the initial treatment period. After 16 weeks, participants will either continue on the same dose or switch to a modified dose based on the study plan. Galvokimig and placebo are given as injections, and the study is designed to be double-blind, meaning neither participants nor researchers know who receives which treatment during the initial phase. During the study, participants will be regularly evaluated for changes in their eczema severity, itch intensity, and overall response to treatment using specific scales like the Eczema Area and Severity Index EASI and Peak Pruritus Numerical Rating Scale PP-NRS. Safety is closely monitored through reports of adverse events up to week 58. The study lasts at least 16 weeks with ongoing assessments to track treatment effects and safety over time.

Researchers are evaluating the effects of zorevunersen, an investigational antisense oligonucleotide medicine, in children with Dravet syndrome, a rare epilepsy disorder caused by reduced Nav1.1 protein due to SCN1A gene mutations. This Phase 3, global, randomized, double-blind, sham-controlled study aims to assess the safety, tolerability, and potential to modify the disease by increasing Nav1.1 protein levels from the nonmutant gene copy. The study also measures changes in seizure frequency, behavior, cognition, clinical status, and quality of life. Participants are randomly assigned to one of two groups for Treatment Period 1, lasting about 52 weeks either receive zorevunersen or undergo a sham procedure without drug administration. Zorevunersen is given by intrathecal injection at specific days and doses during this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen at defined intervals and doses. Patients may also join an open-label extension study if they meet criteria after the main study. Throughout the study, patients will be monitored regularly to assess seizure changes at weeks 28 and 52, as well as adaptive behavior using the Vineland-3 scale. Safety and tolerability are closely followed with standardized evaluations. The study lasts at least 84 weeks, including both treatment periods. Researchers aim to understand how zorevunersen may impact major motor seizures and overall functioning in children with Dravet syndrome.

Researchers are evaluating the safety of LY3954068 in people with early symptomatic Alzheimers Disease. This study also examines how much of the drug enters the bloodstream and its effects on Alzheimers markers. It is a Phase 1 trial sponsored by Eli Lilly and Company focused on participants aged 50 to 85 years with early signs of the disease. The study includes two parts Part A and Part B. In Part A, each participant receives a single dose of LY3954068 or placebo injected into the spinal fluid. In Part B, participants receive two doses of either LY3954068 or placebo administered the same way. There is an optional bridging period after Part B where participants may receive LY3954068 in a separate study. Part A lasts about 45 weeks including screening, and Part B lasts about 100 weeks including screening. Participants will undergo regular assessments such as safety monitoring for adverse events related to the study drug, blood and spinal fluid sampling to measure drug levels and effects on tau proteins, and imaging with Flortaucipir F18 PET scans for tau pathology. Cognitive tests like the Mini Mental State Examination and Clinical Dementia Rating will be used. Safety and drug effects will be followed up to 24 weeks in Part A and up to 52 weeks in Part B, with additional monitoring during the bridging period if chosen.

Researchers are collecting long-term safety and effectiveness data for participants treated with ibrutinib, a first-in-class, orally taken medicine that targets Brutons tyrosine kinase. The study focuses on individuals who have already been treated with ibrutinib in prior studies and are continuing to benefit from the treatment. The goal is to provide ongoing access to ibrutinib while monitoring health outcomes over time. Participants will continue taking ibrutinib capsules once daily at the dose established in their previous study ranging from 140 mg to 560 mg until the doctor decides the treatment is no longer helping, the participant chooses to stop, or other specified reasons occur. Some participants may receive ibrutinib alone or in combination with nivolumab depending on their prior treatment. The study is open-label, meaning everyone knows the treatment being given. During the study, participants are regularly monitored for safety and disease changes through assessments and visits until they stop the study drug or move to other treatments. Researchers track side effects up to 30 days after the last dose and may analyze how the disease responds in combination with earlier study data. The study continues until all participants transition off study treatment or the sponsor ends the trial, ensuring ongoing care and data collection over time.

Researchers are evaluating the long-term efficacy and safety of mirikizumab in children and adolescents with moderate-to-severe ulcerative colitis UC or Crohns disease CD. This Phase 3, open-label, multicenter study aims to understand how well mirikizumab works over an extended period, lasting about 172 weeks with up to 44 visits. The study is sponsored by Eli Lilly and Company and includes participants aged 2 to 19 years who have previously been treated with mirikizumab in earlier studies. Participants receive mirikizumab administered subcutaneously under the skin, with dosing based on their weight. There are multiple doses, numbered Dose 1 through Dose 6, with an additional intravenous rescue dose available if a participant loses response to the treatment. The study follows an open-label design without randomization or masking. Throughout the study, participants undergo regular assessments including clinical remission and response measured by the Modified Mayo Score for UC and the Pediatric Crohns Disease Activity Index for CD at Week 52. Other outcomes include endoscopic remission and response, corticosteroid-free remission, and changes in inflammatory markers. Safety is monitored continuously, and additional treatment may be offered during a continued access period. The total participation time can last over three years, with extensive follow-up visits and evaluations.

Researchers are evaluating whether two drugs, retatrutide and tirzepatide, can prevent serious liver problems in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized clinical trial plans to enroll about 4,500 adults and will last approximately 224 weeks, including up to 25 to 30 clinic visits to monitor health and liver disease progression. The study is sponsored by Eli Lilly and Company. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. After completing the main study, eligible participants may join a 2-year extension where everyone receives either retatrutide or tirzepatide, regardless of their original group. This Master Protocol evaluates multiple pharmacologic agents under controlled conditions. Throughout the study, participants will undergo various assessments including liver function tests, imaging to measure liver stiffness and fat content, and body weight measurements. Researchers will track the time to major adverse liver outcomes and cardiovascular events. Safety and disease progression will be closely monitored, and the study includes evaluations at baseline, week 104, and up to study completion.