Clinical Research Directory

Semaglutide vs Sitagliptin

The effect of once daily dosing of oral Semaglutide versus once daily dosing Sitagliptin on glycemic control, body weight, and safety and tolerability will be compared in Liver Transplant Recipients with poorly-controlled Diabetes Mellitus.

The Effects of Glucagon on Hepatic Metabolism

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

Evaluate the Efficacy and Safety of LivPhcD Capsules in the NAFLD Subjects

Non-alcoholic fatty liver disease (also called NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse. Early-stage NAFLD does not usually cause any harm but nonalcoholic steatohepatitis (NASH) can lead to serious liver damage, including fibrosis or cirrhosis. Nearly 25% of the world's population is affected by NAFLD. There are no FDA-approved medications for the treatment of NAFLD currently and although lifestyle modifications with appropriate diet and exercise have been shown to be beneficial, this has been difficult to achieve and sustain for the majority of patients. LivPhcD™ capsule have shown hepatoprotective effects in both animal and human data. This study aims to investigate the effects of LivPhcD™ capsule in hepatocellular lipid content using Fibroscan.

A Clinical Study of Efinopegdutide in People With Compensated Cirrhosis Due to Steatohepatitis (MK-6024-017)

Researchers are looking for ways to treat a type of liver disease caused by elevated liver fat, called metabolic dysfunction-associated steatohepatitis (MASH). MASH was formerly called non-alcoholic steatohepatitis (NASH). Researchers want to learn if a study medicine called efinopegdutide can treat MASH.The goals of this study are to learn: * If efinopegdutide can lower the amount of fat, inflammation, and scarring (fibrosis) in the liver * About the safety of efinopegdutide and how well people tolerate it

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).

Lifestyle Modification in the Treatment of NAFLD.

The project will study the impact of individually tailored lifestyle counselling compared to standard care on the parameters of NAFLD/NASH in patients with metabolic syndrome. The factors affecting the outcome (including clinical and laboratory parameters and microbiome profiling) will be evaluated.

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.

Effect of Amino Acids on Hepatic Fat Content in Adolescents (AMINOS Study)

Participants 13-18 years of age with extra fat stored in the liver will be randomly assigned to a protein supplement or placebo "fake supplement" for 2 months to see if the participants who get the protein supplement have less fat in the liver compared to participants who were in the placebo group. After the 2 month intervention, all participants can continue the study and will all receive the protein supplement for an additional 10-months.

A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)

Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.

NASH AMPK Exercise Dosing (AMPED) Trial

There is no known cure or regulatory agency approved drug therapy for nonalcoholic fatty liver disease (NAFLD), the leading cause of liver disease worldwide, and its progressive type, NASH. This places increased importance on using exercise to treat NAFLD. While physical activity is recommended for all with NAFLD, how to best prescribe exercise as a specific treatment remains unknown, including what dose of exercise is most effective.

Pathogenesis of Pediatric Nonalcoholic Fatty Liver Disease (NAFLD)

The main aim of the study is to discover the mechanisms underlying the pathophysiology of NAFLD in obese youth.

The Impact of Pectin Supplementation on Systematic Inflammation Pathway, Gut Microbiome, and Metabolic Health in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

The goal of this clinical trial is to learn if daily supplementation with Low-methoxy (LM) pectin (polysaccharides extracted from citrus peels), which are commonly found in the UK diet (not pharmacological agents), can reduce systemic inflammation and improve gut microbiota composition in adults recently diagnosed with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The main question it aims to answer is: -How does dietary Low-methoxy (LM) pectin supplementation affect systematic inflammation pathways such as those mediated by gut microbiota composition and what are the impacts on general metabolic indicators in individuals with MASLD? Researchers will compare a group taking 15g of LM-pectin with 10g of cocoa powder to a placebo group receiving 10g of placebo with 10g of cocoa powder to see if LM-pectin has measurable effects on inflammation and gut microbiota. Participants will: * Take a daily supplement for 6 weeks: either 15g of LM-pectin with 10g of cocoa powder (intervention), or 10g of placebo with 10g of cocoa powder (control) * Provide stool and fasting blood samples before and after the intervention * Undergo anthropometric measurements (weight, height, waist/hip ratio, and blood pressure) * Complete a case report form (CRF) including demographics and health/medical history * Undergo a FibroScan™ to assess liver health * (Optional) Participate in MRI scans to evaluate gut permeability

Prospective Cohort and Biobank of Patients With Nonalcoholic Fatty Liver Disease

The goal of this observational study is to establish a unified cohort for retrospective and prospective high quality baseline and follow-up data registration of patients with a diagnosis of NAFLD/NASH/MAFLD, according to standardized criteria. This will allow future studies aimed at elucidate clinical presentation, natural history, response to treatment, genetic and metabolic risk factors, treatment options and outcomes of the disease. The cohort will allow investigators to carry out genetic, serological, microbiologic and immunological studies.

GLP-1 RA on Liver OMICS in MASLD

In patients with type II diabetes mellitus (T2DM) and obesity, an excess plasma-free fatty acid is found with an associated increased lipid accumulation in adipocytes and liver tissue. Lipid droplet accumulation in the hepatocytes is an initial step in the development of metabolic dysfunction associated steatotic liver disease (MASLD. Insulin resistance, which is associated with T2DM, mediates the inflammation of these lipids, resulting in the progression of MASLD to metabolic dysfunction associated steatotic hepatitis (MASH). Hence, in T2DM, obesity, and MASLD, changes in the lipid profile occur, and they are interrelated. In this study, we aim to assess improvement in the lipidomic, its associated metabolic changes and evaluate the co-regulated genes in the liver tissue among patients with MASLD with intervention with GLP-1 RA, which has shown to benefit T2DM and obesity.

Reversal of Lipid-Induced Insulin Resistance

The purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes. Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).

Short and Long Term Clinical and Patient-Reported Outcomes Associated With Intragastric Balloon Placement in Patients With Nonalcoholic Fatty Liver Disease

This study aims to enroll a robust cohort of NAFLD patients who undergo Intragastric Balloon placement through a multidisciplinary program approach to evaluate clinical and patient-reported outcomes for at least one-year post-placement.

Randomized Double Blinded Placebo-Controlled w/Semaglutide to Prevent Weight Gain After Liver Transplant

In this study, semaglutide will be compared to placebo (a look-alike inactive substance, a "sugar pill") to determine if its use will prevent weight gain after liver transplantation (LT). In addition, researchers will be testing to determine if semaglutide prevents the development of Non-Alcoholic Fatty Liver Disease (NAFLD) after transplant through Magnetic Resonance Imaging (MRI) and laboratory results.

Bicalutamide Therapy in Young Women With NAFLD and PCOS

Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and scarring is projected to be the leading cause of cirrhosis in the United States (U.S.) within the next few years. Women are at disproportionate risk for NASH, with approximately 15 million U.S. women affected. There is an urgent need to understand risk factors for NASH and its progression in women, and sex hormones may provide a missing link. This study will study the contribution of androgens to liver injury and progression in PCOS and mechanistic role of dysregulated lipid metabolism and visceral adiposity in this process. Such findings will provide the rationale for future efficacy studies evaluating selective androgen receptor (AR) antagonism for NASH in PCOS, or alternatively, the need to directly target visceral adiposity or lipid-specific pathways as part of a precision medicine approach to halt fibrosis progression in the nearly 5 million young women with PCOS and NAFLD in the U.S., who remain at increased risk for early onset and progressive liver disease.

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.

Preoperative Ketogenic Diet for Reduction of Hepatic Steatosis

Non-alcoholic fatty liver disease is becoming increasingly common in Canada and throughout the world. Fatty liver can increase the risks of perioperative complications for those who need liver surgery. A ketogenic diet is low in carbohydrates and can be very effective in reducing liver fat content. The purpose of this randomized control trial is to compare the effect of a short duration (4 week) preoperative ketogenic diet on operative and disease outcomes in patients undergoing liver surgery. One arm will be randomized to the ketogenic diet and the other will receive standard of care pre-operative dietary consultation.

Effects of Phytosterol Supplementation on Liver Function and Inflammatory Status in Patients With Nonalcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is considered one of the most common chronic liver diseases worldwide, it recently became a worldwide problem with high morbidity which requires further attention. The use of natural bioactive products such as phytosterols have shown anti-NAFLD effect with little to no side effects when used as a supplement in the therapeutic protocol of NAFLD, in many animals, and In vitro studies. Although the positive impacts of phytosterols on the prevention of hypercholesterolemia and improving liver functions have been reported in previous studies, further clinical experiments, especially human studies are needed to assure the effectiveness of phytosterols on improving liver enzymes, lipid profile, and insulin response in patients with NAFLD. In this study, we focus on the efficacy of phytosterol in a dose similar to the therapicutic lifestyle changes diet (TLC) recommendation with an aim to include it in the therapeutic protocol for NAFLD and to study the effect of some confounders that were excluded in previous studies on this relationship.

Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals

The investigators will conduct a proof-of-principle 4-weeks low-calorie diet (LCD) intervention study in low birth weight (LBW) subjects and normal birth weight (NBW) controls with documented (MR scan) liver fat content equal to or above 5%. The investigators will provide extended in-depth mechanistic insight into the role of impaired subcutaneous adipose tissue (SAT) expandability in ectopic fat deposition before and after LCD.

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).

Influence of a Mediterranean Diet Combined With a Physical Activity Intervention, on NAFLD and Inflammation Parameters.

The study in question is an interventional study with nutritional intervention. The aim of the study is to evaluate whether the adoption of two different models of Mediterranean Diet, based on the different percentage of carbohydrates and lipids, associated with a program of moderate intensity aerobic physical exercise, in patients with obesity and NAFLD can exercise, after only 3 months, effects on: * specific aspects associated with NAFLD, such as the degree of hepatic steatosis and fibrosis; * circulating levels of molecules correlated with the degree of generalized and hepatic inflammation and the blood concentrations of metabolic and cardiovascular risk factors associated with abdominal obesity; * intestinal barrier; * body composition; * intestinal microbiota; * symptoms of IBS (irritable bowel syndrome) in patients with NAFLD.