Clinical Research Directory

RE and Probiotics in MAFLD/NAFLD

This project aims to evaluate the roles of the autonomic nervous system (ANS) and gut microbiota as correlates of clinical improvement in metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD) in response to a therapeutic regimen comprising resistance exercise and probiotic supplementation. The primary objective is to investigate the effects of these non-pharmacological interventions on MAFLD/NAFLD and to identify patient phenotypes based on baseline ANS profiles and gut microbiota composition that predict clinical responses.

A Study to Evaluate DD01 in Overweight/Obese Subjects With MASLD/MASH

This is a Phase 2 Study to evaluate the effect of DD01 treatment in overweight/obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH).

Study to Evaluate the Efficacy and Safety of K-877-ER and CSG452 in Participants With NASH With Liver Fibrosis

A study to investigate the use of combination therapy with two investigational products for the treatment of adult patients with Nonalcoholic steatohepatitis (NASH).

Trial of CS060380 Tablets for Non-alcoholic Steatohepatitis (NASH)

The goal of this clinical trial is to learn if CS060380 tablets works to treat non-alcoholic steatohepatitis(NASH) in adults.It will also learn about the safety of CS060380 tablets.The main questions it aims to answer are: * After 12 weeks of administration, what was the percentage change in fat content evaluated by MRI-PDFF compared to the baseline？ * What medical problems do participants have when taking CS060380 tablets? Researchers will compare CS060380 tablets to a placebo (a look-alike substance that contains no drug) to see if CS060380 tablets works to treat NASH. Participants will: * Take CS060380 tablets or a placebo every day for 12 weeks * Visit the clinic for checkups and tests at the frequency required by the protocol * Keep a diary of their symptoms and the number of tablets taken

An Imaging-based Quantitative Biomarker Assay for NAFLD in Children

This study will validate recently developed Magnetic Resonance Imaging (MRI) and Ultrasound (US) based methods for liver fat quantification in children with obesity and healthy range of body mass index (BMI).

Evaluation of Risk of hEpatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the second cause of cancer-related mortality worldwide. Nonalcoholic fatty liver disease (NAFLD), that is hepatic accumulation of fat in excess of 5% not explained by at risk alcohol intake, is projected to become the leading cause of HCC in Western countries within 2025.NAFLD is most frequently caused by insulin resistance due to unhealthy lifestyle. Due to the epidemics of obesity and type 2 diabetes, NAFLD now affects one in three individuals worldwide. NAFLD-HCC frequently develops without overt cirrhosis suggesting that steatosis directly promotes hepatic carcinogenesis.

Digoxin In NASH (CODIN)

Nonalcoholic steatohepatitis (NASH) is a severe subtype of nonalcoholic fatty liver disease (NAFLD) which affects 1 in 3 Americans. The mainstay of treatment for NASH, which was recently renamed metabolic associated steatohepatitis (MASH), involves lifestyle interventions to promote weight loss and to treat comorbidities such as hypertension, hyperlipidemia, and diabetes mellitus. There is thus, a substantial unmet need for pharmacological therapies that are effective for treatment of NASH, especially in those with fibrosis which is the main predictor of disease progression and mortality among NASH patients. The repurposing of presently available drugs would help expedite the search for agents effective in treating NASH. The cardiac glycoside digoxin is currently used in the management of heart failure and supraventricular tachyarrhythmias. The investigators and other groups have demonstrated that digoxin protects the liver from various forms of acute and chronic liver injury. The investigators preliminary data in healthy human subject indicate an immunomodulatory effect of low dose oral digoxin with no adverse side effects. This study proposes to demonstrate the clinical benefits of digoxin on NASH and on liver fibrosis, thus supporting the repurposing of digoxin as treatment for NASH.

To Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BAR502 in Healthy Subjects

First-in-human, single centre, two parts, dose-escalation, parallel-group, safety, tolerability, pharmacokinetic and pharmacodynamic Phase I study. Part A: randomised, double-blind, placebo-controlled, single ascending dose study. Part B: open label, multiple ascending dose study.

Evaluation of Non-Invasive Tests for Metabolic Liver Disease

The Non-Invasive Biomarkers for Metabolic Liver Disease (NIMBLE) study is a comprehensive, multi-year collaborative effort to standardize, validate and advance the regulatory qualification of blood- and imaging-based biomarkers to diagnose and stage Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH). MASH is characterized by liver inflammation accompanied by simultaneous fat accumulation in the liver.

A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)

This study will determine the effect of oral 80 mg resmetirom administered once daily on participants with well-compensated non-alcoholic steatohepatitis (NASH) cirrhosis by measuring the time to experiencing a Composite Clinical Outcome event.

LITMUS Imaging Study

The LITMUS Imaging Study is a prospectively recruited, observational study of patients with histologically characterised non-alcoholic fatty liver disease (NAFLD). It aims to evaluate the diagnostic performance of imaging biomarkers (ultrasound elastography and magnetic resonance biomarkers) against NAFLD histological scores in a cross-sectional analysis and the natural history of NAFLD in a longitudinal study.

Androgens and NAFLD Longitudinal Cohort Study

The researchers want to learn how androgens, a type of sex hormone, might affect nonalcoholic fatty liver (NAFLD) in young women over time. NAFLD happens when fat builds up in the liver which can cause damage to the liver such as inflammation or scarring. Young women with a condition called polycystic ovary syndrome (PCOS) have a high risk for NAFLD, and they often have high androgen levels too. So the researchers are recruiting young women with PCOS as well as those without PCOS, and will compare changes in NAFLD over time between young women with and without PCOS. This study is funded by the National Institutes of Health

Optimizing Noninvasive assessMent Of DysmEtabolic Compensated Advanced Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is responsible for a significant proportion of liver-related deaths and healthcare costs in the United States, accounting for approximately 36% of liver-related deaths and over one billion dollars in annual healthcare expenses. \[PMID: 34863359\] A recent analysis of healthcare costs in Italy showed that out of the 9,729 NAFLD/NASH patients who were hospitalized and analyzed, the vast majority (97%) did not have advanced liver disease, while 1.3% had compensated advanced liver disease (cACLD), 3.1% had decompensated cirrhosis, 0.8% had hepatocellular carcinoma, and 0.1% underwent liver transplantation. The burden of comorbidities was high across all patient cohorts, and patients with cACLD required a greater number of inpatient services, outpatient visits, and the pharmacy fills compared to those without advanced liver disease. As disease severity increased, mean total annual costs also increased primarily due to higher inpatient services costs. In Italy, as in other EU countries, most of the healthcare costs for patients were attributed to NAFLD/NASH-related liver complications. Thus, the optimization of the non-invasive diagnosis of cACLD represents an urgent need in dysmetabolic liver disease. These advancements will play a crucial role in early detection, risk stratification, and effective management of highly prevalent liver diseases such as NAFLD/NASH and their progression.

Secondary and Tertiary Digital Prevention of Non-alcoholic and Dysmetabolic Liver Disease

The prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, Metabolic dysfunction-associated steatohepatitis (MASH), is high and they are increasingly becoming major causes of cirrhosis, hepatocellular carcinoma (HCC), and the need for liver transplantation. Due to the lack of noticeable symptoms during the early stages, the detection of MASLD is often delayed until the disease has advanced. Currently, the treatment options MASLD are limited to lifestyle interventions such as dietary changes and physical activity. Despite the increasing prevalence of MASLD, there are no drugs available on the market specifically for this condition. The goal is to made new model care which integrates the standard clinical procedures with a digital approach, namely a mobile application for patients and a clinical dashboard for healthcare professionals (HCPs), integrated with simple clinical data (anthropometric, laboratory and imaging data). This study wants to test the feasibility of integrating a digital intervention to improve the patient engagement and linkage to care in order to identify the advanced MASLD at earliest stage (secondary prevention) and mitigate the impact of ongoing advanced liver disease helping patients to manage the long-term effect of disease. To achieve this goal the study will leverage on a mobile app named OpenTele in order to test the adherence to lifestyle changes in patient with MASLD and on the connected clinical dashboard. The app aims at integrating the standard clinical practice with digital technologies able to guide and support patients in order to seamlessly integrate secondary prevention strategies in their everyday life with 2 main aims: * to implement a strategy for delay progression of liver disease; * to reduce the effect of cirrhosis (tertiary prevention).

HuHuangLianzonggan Capsule in Subjects With Nonalcoholic Steatohepatitis: a Phase 2 tRial(HHL-HEPAR)

This study will evaluate the efficacy and safety and the best effective dose of HuHuangLianzonggan capsule in subjects with nonalcoholic steatohepatitis.

Precise Evaluation Criteria for Histological Regression of NASH Fibrosis

It is an observational study of NASH patients with a calculated sample size of 220. Liver biopsy-proven NASH fibrosis with stage F2-F4 will be recruited in this study. A second biopsy will be performed after clinical trials or 1-3 years of lifestyle intervention. Patients will be followed up at baseline and every six months with h-CRP, liver function tests, fasting blood glucose, fasting insulin, ferritin, liver ultrasonography, and liver stiffness measurements.

The Impact of Different Carbohydrate Restriction After a Gastric Bypass on the Ketosis and Ketoacidosis

Background: Ketosis after bariatric surgery is a metabolic process that occurs when the body breaks down fat for energy because of not getting enough carbohydrates. Insufficient production of ketone bodies reduces the rate of weight loss, and excessive amounts of ketones can lead to ketoacidosis or liver failure in patients with nonalcoholic steatohepatitis (NASH). The investigators hypothesize that weight loss is directly related to calorie intake, and a significant reduction in carbohydrate content leads to increased ketosis and the risk of ketoacidosis. Objectives: The study aimed to compare the incidence of ketoacidosis and liver failure in patients with NASH with different intakes of carbohydrates in the early postoperative period after gastric bypass. In addition, the investigators want to find out how carbohydrate restriction will affect weight loss for up to 1 year.

DIAbetes and NAFLD

Non-alcoholic hepatic steatosis (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver and is often associated, in the absence of significant alcohol consumption, with insulin resistance and metabolic syndrome with which it shares the most frequent clinical manifestations (hypertension, dyslipidaemia, visceral adiposity, glucose intolerance). Due to the pandemic spread of obesity and diabetes and by virtue of better control of viral hepatitis, NAFLD is the most common cause of liver damage in Western countries with a prevalence of around 20-30% of the general population. The clinical impact of NAFLD in diabetes is considerable and represents a real driver of the major clinical outcomes that impact on the health of the individual, consequently creating a real 'burden of disease' especially in those populations considered to be at higher risk of disease severity. Individuals with diabetes are, in fact, those at greatest risk of developing the clinical sequelae of NAFLD and often do not receive adequate hepatological support and a correct hepatic pathology. In fact, it has been documented in the literature that the presence of diabetes increases the severity of liver damage, bringing the risk of NASH up to 80% and increasing the risk of significant fibrosis to 30-40% of subjects with hepatic steatosis as well as representing an independent predictor for significant fibrosis. Lastly, the increased risk of hepatocarcinoma in subjects with diabetes and NAFLD should not be overlooked, as documented by our group and confirmed in a large Italian case series. In subjects with diabetes, moreover, the presence of NAFLD is not only associated with worse glycaemic control, but also with micro- and macro-vascular complications as well as nephrological and neuropathic complications and increased mortality. Therefore, the possibility of applying the non-invasive fibrosis scores currently available for NAFLD on a large scale, in a population at high risk of progressive liver disease, would make it possible to characterise (a) the true epidemiology of significant fibrosis (F3 or higher); (b) allow primary prevention actions to be carried out by optimising the use of resources or by identifying subjects at greater risk of damage progression; (c) understand, in cases with a long history of disease the true prevalence of clinical outcomes; (d) understand the epidemiology of comorbidities and polypharmacy as a function of significant fibrosis.

Role of the Very Low Calorie Ketogenic Diet (VLCKD) in Patients With Non-Alcoholic Steatohepatitis (NASH) With Fibrosis

The purpose of the KETONASH study is to evaluate, in patients with metabolic-associated fatty liver disease (MAFLD) with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis, the effect of a very low-calorie ketogenic diet (VLCKD) compared to that of a standard low-calorie diet (standard Mediterranean LCD - in accordance with the European Association for the Study of the Liver/European Society for Clinical Nutrition and Metabolism guidelines on MAFLD/NAFLD).

Study Consortium for Evaluation of RNPC Program in Obese and Overweight Patients (SCOOP-RNPC)

The investigators hypothesize that weight loss obtained with the French RNPC weight reduction program is beneficial for the general health of overweight/obese patients in the medium term. The objective of this cohort study is to demonstrate the effectiveness of the RNPC program on the reduction of drug or instrumental treatments (for example, continuous positive pressure ventilation for the treatment of sleep apnea syndrome) and the improvement of overweight/obesity-associated comorbidities in the medium term. This is a multicenter clinical study, as part of routine care, with standardized nutritional care (RNPC Program) in all RNPC centers in France. A cohort will be formed based on the clinical and biological data usually collected in the centers, enriched by data from additional clinical and biological examinations as well as by self-questionnaires completed by the participants. About 10,000 overweight or obese participants will be included for 2 years and followed 5 years. The SCOOP-RNPC study will have benefits for individual participants, for the scientific community in terms of knowledge acquired and for society with a better definition of the impact of treatments. Responding to the major public health issue represented by overweight, this prospective cohort of overweight or obese patients will make it possible to evaluate, in real-life conditions, the effects of weight loss obtained by the RNPC Program in the short, medium and long term on biological parameters predictive of cardiometabolic risk, drug consumption, quality of life, diet and eating behavior, sleep, physical activity, stress/anxiety, as well as depression. This cohort will make it possible to identify clinical phenotypes and biomarkers to optimize the personalization of the management of overweight or obese patients, in particular those at risk of developing comorbidities associated with excess weight.

The European NAFLD Registry

The European NAFLD Registry is a prospectively recruited, observational study supporting the study of the clinical phenotype, natural history, disease outcomes and pathophysiology of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. The ultimate goals are to better understand the drivers of interpatient variation in disease pathophysiology and severity and to utilise this information to develop and validate biomarkers that, singly or in combination, enable detection and monitoring of disease progression and/or from NAFL through NASH to fibrosis and cirrhosis.

THE FRENCH NATIONAL NAFLD COHORT (FRench pAtients With MEtabolic Steatosis)

The main objective of this cohort study is to determine genetic, clinical biologic and metabolic factors associated with patient heterogeneity in regards to severity of NAFLD at diagnosis as well as during the clinical course. * at diagnosis, with the aim to better characterize patients of different severity and improve our understanding of clinical and histological heterogeneity at diagnosis * during the clinical course to better understand and predict disease progression in terms notably of fibrosis progression and progression to cirrhosis