Clinical Research Directory

Deciphering the Mechanisms Involved in Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis

Background: \- Hepatitis C infection (HCV) is a leading cause of liver disease. Normal bacteria from the intestines may spread to the liver and blood during liver disease. This is called bacterial translocation (BT). Researchers think BT may cause liver disease to worsen. Objectives: \- To study the mechanisms involved in BT in early and advanced liver disease. To find out whether BT causes liver disease to worsen. Eligibility: \- People over age 18 with HCV and clinically stable liver disease. Design: * Participants will be screened with medical history and physical exam. They will have blood tests and imaging studies. * Participants will have 2 outpatient visits and a 3-day stay at the clinic. * At visit 1, participants will have urine and blood tests. They will have a magnetic resonance imaging (MRI) scan. A solution will be injected into a vein. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that slides in and out of the cylinder. * At visit 2, a substance will be injected into a vein and swallowed. Participants will then have blood drawn 5 times over 90 minutes. * During the inpatient stay, serial blood tests will be drawn. * Participants will give 2 stool samples and have another MRI. * A needle will be inserted through the chest wall into a vein inside the liver, guided by ultrasound. The blood pressure inside this vein will be measured and blood will be drawn from it. About 1 inch of liver tissue will be removed. * A study investigator will call participants to discuss all test results.

Remote Electrical Stimulation for Pain and Depression Treatment in Cirrhosis

This study is being done to better understand how the study team can treat pain for people with cirrhosis and depression. Enrolled participants on this feasibility study will be randomized to Transcutaneous Electrical Acustimulation (TEA) or sham TEA.

Hepatic Encephalopathy and Albumin Lasting Cognitive Improvement

Hypothesis: Improvement in cognitive dysfunction with IV albumin in patients with cirrhosis with prior HE and MHE lasts for several weeks after albumin infusion has ended, and is due to persistent improvement in inflammatory markers, endothelial dysfunction, albumin function and gut microbial changes. This will be a single-arm, single-blind sequential trial of IV 25% albumin and IV saline over 8 weeks with biological sampling and cognitive and health related quality of life (HRQOL) testing with each subject acting as their own control.

Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease

The purpose of this research study is to test the safety, tolerability, and effectiveness of the capsules that contain bacteria from healthy individuals when used to treat alcohol craving and drinking.

Empagliflozin in Patients With Cirrhosis and Ascites

A proof-of-concept placebo-controlled trial to explore the acute and 14-day effects of empagliflozin on natriuresis and total body water in patients with cirrhosis and ascites. We will additionally investigate its effect on neurohumoral activation, and renal hemodynamics.

Droxidopa to Increase Mean Arterial Pressure in Decompensated Cirrhosis Patients With Acute Kidney Injury

This study tests whether a medication called droxidopa can help improve blood flow to the kidneys in people with liver cirrhosis who develop kidney problems while in the hospital. When someone with cirrhosis experiences kidney injury, having better blood pressure can help their kidneys recover. Droxidopa is an oral medication that may help raise blood pressure without requiring intensive care or invasive treatments. The study will compare droxidopa to a placebo (inactive pill) in 75 people hospitalized with cirrhosis and kidney injury. Participants will take either droxidopa or placebo pills for 28 days and be monitored for an additional 30 days. Researchers will measure changes in blood pressure and kidney function to determine if droxidopa is effective and safe for these patients. This research could identify a new treatment option for a serious complication of liver disease.

InAdvance: Surveillance, Prevention, and Interception in a Population at Risk for Cancer

This research study is creating a way to collect and store specimens and information from participants who may be at an increased risk of developing cancer, or has been diagnosed with an early phase of a cancer or a family member who has a family member with a precursor condition for cancer. * The objective of this study is to identify exposures as well as clinical, molecular, and pathological changes that can be used to predict early development of cancer, malignant transformation, and risks of progression to symptomatic cancer that can ultimately be fatal. * The ultimate goal is to identify novel markers of early detection and risk stratification to drive potential therapeutic approaches to intercept progression to cancer.

Screening Cardiometabolic Opportunities Using Transformative Echocardiography Artificial Intelligence (SCOUT Echo-AI)

The goal of this prospective, multicenter, open-label, blinded end-point pragmatic study is to evaluate an artificial intelligence (AI)-augmented echocardiography screening approach for early detection of metabolic dysfunction associated steatotic liver disease (MASLD) and/or cirrhosis, in patients undergoing routine transthoracic echocardiograms (TTEs). The main question it aims to answer is to: 1. Evaluate notification responsiveness and rates of confirmatory testing for patients identified as high risk for having liver disease to determine whether optimized notifications increase timely confirmatory testing and treatment initiation versus standard of care assessment. 2. Compare time to diagnosis, treatment uptake, and clinical outcomes (hospitalizations, incident ASCVD, mortality) between cohorts identified as high risk by the AI algorithm and comparison groups to determine whether AI guided screening shortens time to diagnosis and increases appropriate treatment.

Allopurinol Versus Atorvastatin to Prevent Complications of Liver Cirrhosis

The study aims to compare the potential benefit of allopurinol versus atorvastatin in reducing the risk of developing cirrhosis-related complications, delaying the onset of hepatocellular carcinoma, and improving survival. Furthermore, the study aims to evaluate their impact on parents' related quality of life.

Adverse Outcomes and Mortality in Liver Transplant

Prospective natural history pilot study to explore the link between muscle composition using an MRI-based Muscle Assessment Score (MAsS) and adverse outcomes in liver transplant candidates.

Getting To Implementation: Improving Cancer Screening for Veterans

Gastrointestinal cancers such as colon cancer and liver cancer cause many deaths in the US. Testing could catch these cancers early, helping people live longer. The goal of this study is to compare two different ways of getting more people tested for these cancers: 1) by directly reaching out to the people who need testing or 2) by helping providers fix issues that hold up testing. The main question it aims to answer is: how should healthcare systems go about choosing one or the other? Researchers will look at cancer testing rates over time at sites that are trying these different approaches. They will also survey and interview participants from these sites.

Affect of Melatonin on Sleep and Cognition in Cirrhosis

The goal of this clinical trial is to learn the affect of melatonin on sleep, cognitive function, and quality of life (QoL) in patients with cirrhosis and a complication called hepatic encephalopathy (HE). The main questions this study aims to answer are: * Does taking melatonin increase REM sleep, an important part of healthy sleep that is reduced in cirrhosis? * Does taking melatonin improve cognitive function and reported QoL? This is a pilot study, where participants will: * take one month of melatonin, followed by one month of thiamine, which is another supplement but is not suspected to impact sleep significantly. * Undergo cognitive testing and take surveys * Wear a commercial wearable sleep tracker * Have a formal sleep study and salivary melatonin collection at the end of taking each supplement at our sleep center Participants will be blinded, and neither they nor the researchers will know which supplement they are taking first and which they are taking second. They will also be randomized, with half starting with melatonin and the other half starting with thiamine.

Hepatic Impairment With Cirrhosis Due to Cholestatic Liver Disease

A Phase 1, Open-label Extension Groups Study in Subjects having Hepatic Impairment with Cirrhosis due to Cholestatic Liver Disease

LiverSleep: A Behavioral Sleep Intervention for Patients With Cirrhosis and Insomnia

This is a pilot trial to test the feasibility and acceptability of a virtual cognitive behavioral program for insomnia for patients with cirrhosis.

Evaluation of Cirrhotic Cardiomyopathy by Cardiac MRI in Patients Waiting for Liver Transplant.

The aim of this multicenter prospective interventional pilot study is to describe the evolution of myocardial fibrosis in cirrhotic patients before and after liver transplantation (LT). Through multimodal analysis of myocardial function and architecture, and analysis of specific markers of inflammation, we aim to explore the following hypotheses: 1) systemic inflammation promotes myocardial fibrosis in cirrhotic patients and could be an early marker of cirrhotic cardiomyopathy; 2) LT allows resolution of myocardial fibrosis by preventing the bacterial translocation that favors the development of deleterious systemic inflammation.

Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis

This phase II trial studies how well simvastatin works in preventing liver cancer in patients with liver cirrhosis. Simvastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Prehab and Creatine/Whey Supplementation in Frailty Among Patients With Cirrhosis

Frailty and muscle health are important for patients with chronic liver disease. This study looks at the use of a digital prehabilitation app (HEAL-ME) plus creatine and whey protein combination supplementation on maintaining muscle health in patients with liver disease. The investigators anticipate that this combination of supplementation and nutrition/exercise prehabilitation app will maintain muscle health in patients with liver disease.

Technology Enabled Strategies to Promote Treatment Adherence in Liver Transplant

Liver transplantation is increasingly performed for older adults with multiple comorbidities. Medication adherence is key to maintaining proper function of the transplanted liver and optimize health; however, adhering to post-transplant treatment is complex. This trial will study how available technology combined with transplant center resources and caregiver support can optimize medication adherence, quality of life, and health outcomes among new liver transplant recipients at 3 centers.

Inferior Vena Cava Pressure as Alternative to Hepatic Venous Pressure for EUS-guided Portal Pressure Gradient Measurement

This study investigates a new, simplified approach to measuring blood pressure within the liver (portal hypertension) using Endoscopic Ultrasound-Guided Portal Pressure Gradient Measurement (EUS-PPG). While this minimally invasive method traditionally relies on a hepatic vein as the baseline reference point, advanced liver scarring can make these veins twisted and highly difficult to access. To address this challenge, our study evaluates the Inferior Vena Cava (IVC)-the body's largest main vein-as an alternative reference site. Currently, it remains scientifically unproven whether the inferior vena cava or the hepatic vein provides the more reliable and accurate pressure reading for calculation, as anatomical distortion from cirrhosis can affect both areas differently. By measuring and comparing both venous compartments during a single, clinically scheduled endoscopy session, this study aims to determine if the pressures are truly interchangeable. Ultimately, this research will clarify which vessel serves as the optimal reference point, helping to establish a safer, more reliable diagnostic standard for patients with complex vascular anatomy.

Prevalence of Pain in Hospitalized Cirrhotic Patients

According to the WHO, pain is an "unpleasant sensory and emotional experience, linked to existing or potential tissue damage, or described in terms suggestive of such damage". It is a legal obligation to evaluate and take care of it (law of 03/04/2022). However, there are still areas where this is not addressed, particularly in cirrhotic patients (Piano V et al. 2023). The global prevalence of cirrhosis increased by 74.53% between 1990 and 2017 (Liu YB et al, 2022, INSERM France file and Zhai M et al. 2021). In France, the prevalence of cirrhosis is estimated to be 200,000 patients (Cohorte Constances 2017; Serfaty 2019). The causes are varied: toxic (alcohol), viral (hepatitis B, C, HIV), genetic (hemochromatosis, primary biliary cirrhosis) but also iatrogenic or linked to a metabolic syndrome, non-alcoholic fatty liver disease. The first symptoms of cirrhosis are fatigue, loss of appetite and weight, nausea and vomiting, discomfort and abdominal pain. More serious symptoms may appear such as depression, confusion, sleep disturbances, edema of the lower limbs, ascites, severe pruritus or jaundice. All of these symptoms can be the cause of the pain. However, to date, there are no studies in France on the epidemiology of pain in patients with cirrhosis (Piano V et al. 2023, Klinge M, et al, 2018). To evaluate the prevalence of pain in cirrhotic patients hospitalized at the Center Hospitalier de la Dracénie in Draguignan. Patients hospitalized at the Dracénie CH with a diagnosis of cirrhosis in its patients will be identified in the various departments by a referring doctor who will have to contact Dr PIANO. The latter, as investigating doctor, will then be able to select the patients meeting the inclusion criteria of the protocol and the informants of the existence of the research. He will explain the study to them in detail, give them sufficient time for reflection before obtaining their oral agreement and giving them the information-no-opposition letter. The research will require a single consultation lasting between 15 and 45 minutes. During the visit, the patient will be asked whether or not they are experiencing pain.

Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis

This seamless, adaptive, two-stage, Phase 2b/3, randomized, double-blind, multicenter, parallel-groups, placebo-controlled study will assess the efficacy, safety, and tolerability of belapectin compared with placebo in patients with nonalcoholic steatohepatitis (NASH) cirrhosis and clinical signs of portal hypertension but without esophageal varices at baseline.

Screening for Alcohol-related Cognitive Impairments in Cirrhotic Patients

80% of patients with alcohol use disorders (AUD) present cognitive impairments, such as memory and executive functions. These disorders may have repercussions in addiction treatment by altering the patient's adherence to care. The level of impairment is dependent on the onset of addiction, and also the duration of abstinence. A complete neuropsychological evaluation is necessary to highlight cognitive impairments. In practice, the evaluation of these disorders by practitioners, is done with the help of tools of screening like the MoCa (Montreal cognitive assesment) and the BEARNI (Brief evaluation of alcohol related neuropsychological impairment). However, none of these tools have been evaluated in patients with alcoholic cirrhosis. Indeed, some studies have suggested that liver disorders including cirrhosis may be a factor aggravating cognitive disorders. The purpose of this study is to evaluate the ability of the BEARNI tool to detect alcohol-related cognitive problems in patients with alcohol-related cirrhosis.

Evaluation of a Modified Bowel Preparation Regimen in Cirrhotic Patients Undergoing Colonoscopy

Inadequate bowel preparation compromises colonoscopy quality and diagnostic accuracy, and cirrhosis is a recognized independent predictor of poor bowel cleansing. However, no bowel preparation regimen has been prospectively validated or specifically tailored for cirrhotic patients. This multicenter, prospective, randomized, single-blind controlled clinical trial will evaluate whether the addition of adjunctive measures as an intensified bowel preparation protocol improves bowel cleansing quality in adult patients with cirrhosis undergoing elective outpatient colonoscopy. Participants will be randomized 1:1 to receive either a standard bowel preparation protocol, consisting of a 2-litre split-dose polyethylene glycol (PEG) regimen combined with a one-day low-residue diet and clear liquids the afternoon before the procedure (control), or the same split-dose regimen with the assigned adjunctive measures: 15 mg bisacodyl, a 3-day low-residue diet, and clear liquids the day before colonoscopy (intervention). The primary outcome is the proportion of patients achieving adequate bowel preparation, defined as a Boston Bowel Preparation Scale (BBPS) total score ≥6 with no individual segment score \<2. Secondary outcomes include polyp, adenoma, advanced adenoma and colorectal cancer detection rates, caecal intubation rate, patient compliance, tolerability, and adverse events. Pre-specified subgroup analyses will evaluate the influence of etiology and severity of cirrhosis and portal hypertension complications. By addressing a critical and unmet clinical need, this trial aims to generate high-quality evidence to optimize bowel preparation strategies in patients with cirrhosis, improve colonoscopy quality, and ultimately enhance colorectal cancer screening outcomes in this vulnerable population.

Zanzalintinib in Second Line and Beyond for the Treatment of Advanced Liver Cancer

This phase Ib/II trial tests the safety, side effects, and best dose of zanzalintinib and how well it works in treating patients with hepatocellular (liver) cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Zanzalintinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Giving zanzalintinib may be safe, tolerable, and/or effective in treating patients with advanced liver cancer.