Primary Sclerosing Cholangitis (PSC)

Researchers are evaluating the binding of a new PET tracer called [68Ga]Ga-DOTA-Cys-ATH001 in the liver and gastrointestinal tract. The study compares healthy volunteers with patients who have metabolically caused steatohepatitis (MASH), fibrostenotic Crohn's 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 PET/MRI 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 participant's 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 mg/kg: 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.

Researchers are evaluating 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 the bile ducts. The study aims to understand the effects of elafibranor in slowing liver damage and reducing serious health risks such as the need for a liver transplant or death. This is a Phase III, randomized, double-blind, placebo-controlled trial sponsored by Ipsen. Participants will be randomly assigned to receive either elafibranor 120 mg once daily or a placebo tablet once daily. The study includes a screening period, a treatment period expected to last up to about 5 years until enough health events occur, and a post-treatment safety follow-up of approximately four weeks. Both treatments are given orally as tablets. During the study, participants will have routine clinical assessments including lab tests, imaging, and patient-reported symptom evaluations to monitor liver disease progression, symptoms like itching and fatigue, quality of life, and safety. Researchers will measure event-free survival from baseline until the end of treatment, and monitor adverse events, physical exams, vital signs, ECG readings, and laboratory parameters. Participants may withdraw at any time and may be involved for several years depending on study progress.

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 1x10^10 CFU per capsule and a high dose of 1x10^11 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 building a comprehensive registry for Hepato-Renal Fibrocystic Diseases (HRFD), which include rare conditions like Autosomal Recessive Polycystic Kidney Disease (ARPKD) and related disorders such as Joubert syndrome and congenital hepatic fibrosis. The goal is to gather clinical and genetic information and create educational resources to help families, doctors, and genetic counselors better understand these diseases. This observational study is designed to support research progress and community awareness through a shared database and biospecimen resources. Participants may choose to contribute to various parts of the study, including a clinical database, genetic testing, tissue donation, and educational resources. Medical records will be reviewed, with data entered into a secure database after removing personal identifiers. Blood or saliva samples may be collected from patients and their parents for genetic analysis, with samples stored at a specialized biorepository. Tissue samples from procedures like nephrectomy or autopsy may also be collected and stored for research. Participants will provide access to their medical information without needing to visit the study center. Data collection includes past, current, and future medical records, with annual updates for ongoing participation. Genetic and tissue samples will be stored and used to support research. The study team monitors the development of this resource over five years to enhance knowledge and treatment options for HRFD. Participation duration varies depending on continued involvement and consent.

Researchers are creating a biobank of specimens and clinical data to help understand cholestatic liver diseases, specifically primary biliary cirrhosis/cholangitis (PBC) and primary sclerosing cholangitis (PSC). This observational study collects information to support current and future research aimed at learning how these diseases begin and progress. Participants include those diagnosed with PSC, PBC, other chronic liver diseases, and individuals without liver disease. Samples of blood, saliva, stool, and urine are collected during visits, through mail-home kits, or remote phlebotomy. Bile samples and bile duct cells are collected only during necessary clinical procedures called ERCPs at Mayo Clinic. During the study, participants provide various biological samples and clinical data. Researchers will monitor the number of participants, types of samples collected, and clinical outcomes over 20 years. This long-term observation helps develop new tests for early detection and better understanding of disease progression.