Primary Sclerosing Cholangitis (PSC)

Researchers are evaluating two types of 12-mm self-expandable metallic stents for treating adults with unresectable malignant distal biliary obstruction, a condition caused by cancers such as pancreatic cancer and cholangiocarcinoma. This clinical trial aims to compare the effectiveness and safety of partially covered versus bare metallic stents, as it is unclear which stent type better prevents recurrent biliary blockage and reduces complications. The study is prospective, randomized, and single-center, focusing on patients who have already undergone percutaneous transhepatic biliary drainage PTBD. Participants will be randomly assigned to receive either a 12-mm partially covered or a 12-mm bare metallic stent, both placed through the existing PTBD tract using a percutaneous transhepatic approach. The stent placement will be followed by careful monitoring. The trial includes two groups one receiving the partially covered stent ComVi Biliary Stent and the other the bare stent Niti-S Biliary Uncovered Stent. The study will follow participants for 12 months after stent placement, with assessments at 3, 6, and 12 months. Throughout the study, participants will undergo evaluations to measure the cumulative incidence of recurrent biliary obstruction, stent patency duration, reintervention rates, overall survival, and procedure-related complications such as pancreatitis, cholecystitis, bleeding, perforation, and cholangitis. These assessments involve imaging and clinical follow-up visits. The outcomes will help guide the choice of the most suitable 12-mm metallic stent for patients with this condition, supporting better treatment decisions over a one-year period.

Researchers are evaluating the binding of a new PET tracer called 68GaGa-DOTA-Cys-ATH001 in the liver and gastrointestinal tract. The study compares healthy volunteers with patients who have metabolically caused steatohepatitis MASH, fibrostenotic Crohns Disease CD, and primary sclerosing cholangitis PSC. This first-in-human, phase 0, multi-center trial aims to understand tracer uptake patterns and assess its safety and distribution in the body. Participants receive a single intravenous injection of up to 100 micrograms of the tracer, followed by PET and MRI scans to visualize tracer binding and body function. Some participants in specific cohorts undergo a second injection and imaging visit within six weeks to test tracer reliability. Blood samples are collected from certain groups to measure tracer levels over time. Safety assessments and remote follow-up calls are also part of the study protocol. During the study, participants will have health checks and eligibility screening before dosing. Imaging includes whole-body PETMRI scans and specific examinations like FibroScan for some groups. Safety is monitored through vital signs, ECG, lab tests, and injection site observations. Follow-up calls check on any side effects or medication use. The trial involves 2 to 3 visits depending on the participants cohort and includes detailed assessments of tracer uptake and pharmacokinetics.

Researchers are investigating the use of 18F-DFA PET imaging to evaluate liver injury, a condition involving rapid liver function decline with symptoms like increased liver enzymes, jaundice, and abdominal discomfort. This observational study aims to assess how accurately this imaging method detects liver damage compared to standard clinical biochemical tests and liver biopsy, which is the current gold standard despite its sampling limitations. The study focuses on adults clinically diagnosed with liver damage or liver failure, exploring the correlation between 18F-DFA uptake in the liver and liver function indicators. Participants diagnosed with liver injury will undergo 18F-DFA PET imaging as part of the study. This radioactive tracer, based on vitamin C structure, is used to visualize liver function non-invasively. The imaging process involves a PET-CT scan lasting about 10 minutes, followed by a one-hour waiting period in the examination room before leaving. The study will compare imaging results with clinical liver function tests or liver biopsy findings to determine the sensitivity and specificity of this method. During the study, participants will have their liver function monitored using PET-CT scans and clinical biochemical markers. The primary outcomes include changes in liver uptake values on PET imaging at 6 months and the relationship between imaging results and standard liver function indicators. Participants will be followed up as needed, with assessments including liver enzyme levels and other blood tests. The total study duration depends on individual follow-up, and safety monitoring will address any issues related to PET imaging procedures.

Researchers are evaluating a new, simple breath test that analyzes volatile organic compounds VOCs in exhaled breath to help detect liver cancer earlier and monitor liver conditions such as cirrhosis and primary sclerosing cholangitis. This study focuses on adults aged 18 and older who have liver cancer, liver cirrhosis, primary sclerosing cholangitis, or tummy symptoms with a normal liver scan. The goal is to improve early detection and monitoring of liver diseases that are often diagnosed too late for effective treatment. Participants will provide a breath sample after fasting for 6 hours during a one-hour appointment at an NHS hospital. They will also answer health questions and allow access to relevant medical records. The study includes groups of participants with liver cancer, benign liver disorders, and healthy controls with non-specific gastrointestinal symptoms but normal liver scans. There are no treatments or drugs involved as it is an observational study. During the visit, researchers will collect breath samples and health information to measure the diagnostic accuracy of the breath test for detecting liver cancer. The breath collection is non-invasive and safe. Participants will not receive direct health benefits from taking part, but the results may help develop an easier way to detect liver disease in the future. The study is led by Imperial College London and takes place in NHS hospitals across the UK.

Researchers are evaluating the safety of siplizumab, an investigational anti-CD2 monoclonal antibody, as an induction immunosuppressive treatment in adult patients with autoimmune liver diseases AILD such as autoimmune hepatitis AIH and primary sclerosing cholangitis PSC undergoing liver transplantation. This pilot, open-label phase 1 study addresses the need for effective therapies to prevent immune-mediated graft injury and complications post-transplant. Siplizumab targets memory T cells involved in rejection and autoimmunity after liver transplantation in these patients. Participants will receive two intravenous doses of siplizumab at 0.6 mgkg one dose intraoperatively on the day of transplant Day 0 and another on Day 4 post-transplant. Up to eight subjects will be enrolled. The study lasts about 15 months, including approximately three months waiting for transplant and 12 months of follow-up after transplantation. During the study, participants will be monitored for serious infections within the first month after transplant and for other outcomes such as immune-mediated liver injury, graft loss or death, rejection episodes, donor-specific antibodies, and disease recurrence over 12 months post-transplant. Assessments will include safety, tolerability, pharmacokinetics, and pharmacodynamics of siplizumab, with ongoing observation throughout the study period.

Researchers are evaluating the drug TAK-781 to determine its safety, tolerability, and how the body processes it in both healthy volunteers and participants with non-cirrhotic Primary Sclerosing Cholangitis PSC. This Phase 1 study aims to understand how TAK-781 affects the immune system and its pharmacokinetics and pharmacodynamics. The study is sponsored by Takeda and involves detailed monitoring of participants responses to the drug. The study includes two main phases Phase 1a and Phase 1b. In Phase 1a, healthy participants receive either a single dose or multiple doses of TAK-781 or a placebo through injections. Different dose levels and regimens are tested across various cohorts, with some cohorts potentially repeated to assess safety and target engagement. In Phase 1b, participants with large duct, non-cirrhotic PSC receive a single dose of TAK-781. The Phase 1b part only starts after completion of the single ascending dose portion of Phase 1a. Participants will be involved for about 36 weeks, during which they will undergo clinical evaluations including laboratory tests, ECGs, and vital sign monitoring to check for treatment-emergent adverse events and any clinically significant changes. Researchers will also measure drug levels in the blood, immune responses, and fibrosis biomarkers. Safety and tolerability will be carefully monitored throughout the study periods, with follow-up visits to assess ongoing effects and adverse events.

This research aims to evaluate how well and safely elafibranor works compared to a placebo in adults with Primary Sclerosing Cholangitis PSC, a rare liver disease that causes inflammation and scarring of bile ducts. PSC can lead to serious liver damage, including the need for liver transplant or death. The study is a Phase III trial involving about 350 adults with large duct PSC, conducted to understand treatment effects over an extended period. Participants will be randomly assigned to take either 120 mg of elafibranor or a placebo tablet once daily. The study includes a screening period, a treatment phase expected to last about five years until enough health events occur, and a post-treatment safety follow-up approximately four weeks after treatment ends. The study is double-blinded and placebo-controlled, ensuring unbiased evaluation of elafibranors effects. During the study, participants will undergo regular clinical assessments, laboratory tests, imaging, and patient-reported evaluations to monitor liver disease progression, symptoms like fatigue and itching, quality of life, and safety. The primary outcome measured is event-free survival from baseline up to five years. Participants may withdraw at any time, and the total duration for each participant may span several years including treatment and follow-up.

Researchers are evaluating the safety and effectiveness of LB-P8 in adults with primary sclerosing cholangitis PSC, a liver condition. This phase 2, randomized, double-blind, placebo-controlled study involves multiple centers and aims to better understand how LB-P8 works in patients with PSC. The study is sponsored by LISCure Biosciences and includes patients aged 18 to 75 years with specific liver-related criteria. The study has two parts Part 1 focuses on testing the safety and tolerability of two doses of LB-P8 a low dose of 1x1010 CFU per capsule and a high dose of 1x1011 CFU per capsule in up to 12 patients. Part 2 compares these two doses of LB-P8 to a placebo in 75 patients randomized equally among the three groups, with treatment lasting up to 24 weeks. Participants will take one oral capsule daily according to their assigned dose or placebo. During the study, participants will undergo various assessments including blood tests to measure liver enzyme levels, liver fibrosis, and other liver function indicators. Researchers will monitor safety, liver disease progression, and the impact of treatment on these measures. The study includes regular visits and evaluations throughout the treatment period, with the goal of understanding both safety and potential changes in liver health over time.

Researchers are building a network called the Autoimmune Liver disease Network for Kids A-LiNK to improve care for children with autoimmune liver diseases such as autoimmune hepatitis AIH and primary sclerosing cholangitis PSC. These conditions present unique challenges in diagnosis and treatment, and there is currently no standard approach for monitoring or managing symptoms. The network aims to create a shared registry and collaborative learning environment to enhance patient-centered outcomes. This observational study involves pediatric patients diagnosed with AIH, PSC, or autoimmune sclerosing cholangitis ASC. There are no treatments or interventions being tested. Instead, the study focuses on collecting clinical data and information about care processes across participating centers, fostering transparent data sharing, and engaging patients and families in research priorities to improve clinical outcomes and quality of life. Participants will contribute clinical measurement data through the shared registry, which will be used to track disease characteristics, relapse rates, complications, steroid side effects, and quality of life using tools like the Pediatric Quality of Life Inventory PedsQL 4.0. The study also examines racial and ethnic disparities. The research will continue through 2034, aiming to advance understanding and care for children and young adults with autoimmune liver disease.

Researchers are studying hepato-renal fibrocystic diseases HRFD, which include rare conditions like Autosomal Recessive Polycystic Kidney Disease ARPKD, Joubert syndrome, Bardet Biedl syndrome, Meckel-Gruber syndrome, congenital hepatic fibrosis, Caroli syndrome, oro-facial-digital syndrome, nephronophthisis, and glomerulocystic kidney disease. The study aims to create a coordinated clinical and genetic database to improve diagnosis, treatment, and research progress by sharing information and biological samples among institutions. Participants can contribute to a clinical database by allowing access to their medical records, which will be anonymized and entered into a shared database. Optional parts of the study include genetic testing through blood or saliva samples from the participant and their parents, as well as donating tissue samples collected during medical procedures or autopsies. These samples will be stored in specialized repositories to support future research. Participants will have their medical records reviewed periodically, with initial data entry and annual follow-ups for the duration of the study or until they choose to withdraw. Genetic and tissue samples will be processed and stored securely. The main outcome is the development and maintenance of a comprehensive translational resource for HRFD over five years. The study does not require clinic visits and involves minimal participant burden while contributing valuable data and materials for ongoing research.