Clinical Research Directory

Simultaneous Quantification of Liver Fat Content, Fatty Acid Composition, and Fibrosis Using Spin-lock MRI for Steatohepatitis Assessment

Non-alcoholic fatty liver disease is a major health problem worldwide. It includes simple steatosis and NASH which has inflammation in the liver, with or without fibrosis. Fat content, fibrosis, and inflammation are three important components to evaluate NASH. Liver biopsy is the current gold standard for the diagnosis of NASH. Liver biopsy; however, is invasive. The existing non-invasive methods still have significant limitations to assess NASH. It was reported that quantification of fatty acid composition is feasible for evaluation of metabolic disorders and inflammatory conditions. However, this measurement cannot be used to evaluate fibrosis. Liver fibrosis is characterized by excessive deposition of collagen-rich connective tissues in the liver, which can be quantified by macromolecular proton fraction (MPF), an MRI parameter reflecting the macromolecular level in tissues. Although it has the potential to directly quantify fibrotic tissue, the effect of inflammation on MPF measurement was not well studied. In summary, NASH assessment using non-invasive imaging methods remains challenging. Based on our previous work of MPF imaging with spin-lock (MPF-SL) and chemical-shift encoding-based water-fat imaging in spin-lock MRI, the investigators will develop a fast acquisition technology to collect data for simultaneous quantification of liver fat content, fatty acid composition, and fibrosis within a single breath-hold less than 14 seconds. Our method does not require extra hardware and does not need to inject a contrast agent. The investigators will evaluate the repeatability and reproducibility of the proposed method on volunteers. To evaluate its clinical value, the investigators will recruit 120 subjects (60 with simple steatosis and 60 with NASH) in this study. The investigators will use histology analysis as the gold standard and evaluate the diagnostic value of our proposed method for detecting NASH. This project will provide a non-invasive diagnostic technology for the assessment of NASH. The proposed MRI technology also has the potential to be applied for other clinical purposes.

Evaluation of Miricorilant on Liver Fat in Patients With MASLD

A Phase 1, Open-Label Study Evaluating the Effect of Miricorilant on Hepatic Lipids in Patients with Presumed Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Non-alcoholic Fatty Liver Disease Parametric PET (FLiPP) Study

The goal of this study is to evaluate non-invasive imaging techniques for determining liver steatosis (fat), inflammation (abnormal tissue swelling), and fibrosis (abnormal tissue scarring).In addition, the study group will be using other test measures including personal demographics, laboratory blood test results, and imaging measurements to determine the severity of NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), inflammation, and fibrosis.

A Physiologic Analysis of Endoscopic Sleeve Gastroplasty (ESG)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Affecting approximately one-third of the United States (U.S.) population, the prevalence of NAFLD increases to 90% in patients with obesity. In 25% of patients, NAFLD progresses to a more severe form-non-alcoholic steatohepatitis (NASH)-which further increases the risks of cirrhosis and hepatocellular carcinoma. In 2017, the lifetime costs of caring for NASH patients in the U.S. were estimated at $222.6 billion, with the cost of caring for the advanced NASH (fibrosis stage ≥ 3) being $95.4 billion. It is projected that the number of NASH cases will increase by 63% from 2015 to 2030. Given the weight loss efficacy of Endoscopic Bariatric and Metabolic Therapies (EBMTs), it has been suggested that EBMTs may serve as a novel treatment category for NASH. Previously, the PI and Co-Is studied the effect of Intragastric balloons (IGB)-the oldest EBMT device-on NASH. EUS liver biopsy performed at the time of IGB removal revealed resolution of all NASH histologic features including fibrosis. A follow-up study by a different group showed similar findings. Furthermore, studies have showed the benefits of S-ESG and Aspiration Therapy (AT) on non-histologic features of NASH. Given the greater weight loss experienced after P-ESG compared to IGB (20% vs 10% TWL) and the more reproducible technique and shorter learning curve of the current P-ESG compared to S-ESG, we aim to assess the effect of P-ESG on NASH.

Meta-Analyses of the Effect of Plant Protein Versus Animal Protein on Cardiometabolic Risk

Vegetarian diets have been associated with a reduced risk of preventable diseases such as type 2 diabetes and cardiovascular disease. These effects may be mediated through direct or indirect pathways. Although the high intakes of nuts, legumes, dietary fibre, whole grains, and unsaturated plant oils have each individually been associated with lower risk of type 2 diabetes and cardiovascular disease, so too has the displacement of red meats, processed meats, and saturated animal fats. One of the most important considerations in moving from animal-based diets to more plant-based diets is the replacement of animal proteins (e.g. meat, fish, dairy, eggs) with vegetable proteins (e.g. legumes, nuts, and seeds). It is unclear whether this particular replacement alone results in advantages for metabolic and cardiovascular health. To improve evidence-based guidance for dietary guidelines and health claims development, we propose to conduct a series of systematic reviews and meta-analyses of the effect of plant-based protein in exchange for animal protein on blood lipids, glycemic control, blood pressure, body weight, uric acid, markers of non-alcoholic fatty liver disease (NAFLD), and kidney function and injury. The systematic review process allows the combining of the results from many small studies in order to arrive at a pooled estimate, similar to a weighted average, of the true effect. The investigators will be able to explore whether the effects of replacing animal-based protein for plant-based protein hold true across different sexes, age groups, and background disease states and whether the effect depends on the protein source, dose, or background diet. The findings of this proposed knowledge synthesis will help improve the health of Canadians through informing recommendations for the general public, as well as those at risk of heart disease and diabetes.

Non-Invasive MASLD Diagnosis & T2D Remission Biomarkers

The goal of this observational study is to prospectively develop and validate a non-invasive scoring system based on metabolic markers, proteomic, and transcriptomic profiles to accurately screen, diagnose, stage, and monitor Metabolic dysfunction-associated steatotic liver disease (MASLD) activity and regression as a replacement for the invasive liver biopsy tool in Bahraini bariatric patients. The study also aims to identify biomarkers for predicting type 2 diabetes mellitus remission post-bariatric surgery. The main questions it aims to answer are: * What proteomic and transcriptomic markers can be used to accurately screen, diagnose, stage, and monitor MASLD activity and regression? * What transcriptomic markers can predict type 2 diabetes mellitus remission? Researchers will compare the proteomic and transcriptomic profiles of bariatric patients before and after surgery to identify molecular changes associated with weight loss and normalization of metabolic biomarkers. The data will be used to design and validate a scoring system for MASLD diagnosis and monitoring. Participants will undergo comprehensive assessments, including anthropometric measurements, metabolic biomarker evaluations, proteomic, and transcriptomic profiling at three time points: before surgery, and at 6- and 12-months post-surgery. The data collected will inform the development of the non-invasive scoring system, which will be tested for its reliability and accuracy in replacing liver biopsy as the standard diagnostic tool for MASLD.

Elucidating Hepatic Metabolism in Non-alcoholic Fatty Liver Disease

The goal of this observational, cross-sectional, case-control clinical study is to investigate the metabolic adaptations underlying the progression of nonalcoholic fatty liver disease (NAFLD), and to test the hypothesis that hepatic mitochondrial reductive stress contributes to progression of NAFLD. The main question it aims to answer is: Do patients with advanced NAFLD compared to patients with mild NAFLD and healthy controls have increased hepatic mitochondrial reductive stress as determined by the ketoisocaproate breath test and by plasma beta-hydroxybutyrate to acetoacetate ratio (b-OHB/AcAc)?

The Ameliorative Effect of C-Kit (+) Hepatic Endothelial Cells With Mertk Deficiency on Nonalcoholic Steatohepatitis

The prevalence of non-alcoholic fatty liver disease (NAFLD) has been steadily increasing, with 10-20% of affected individuals progressing to non-alcoholic steatohepatitis (NASH). NASH is pathologically characterized by hepatic inflammation, steatosis, and hepatocyte injury. Furthermore, this condition carries a significant risk of progression to advanced hepatic fibrosis (pathological Scheuer fibrosis stage F≥3), cirrhosis, and even hepatocellular carcinoma (HCC). In recent years, NASH has emerged as the leading contributor to the growing burden of cirrhosis worldwide, representing a major public health challenge. Despite the high incidence and clinical severity of NAFLD, there are currently no FDA-approved therapeutic agents for its management. Therefore, elucidating the molecular mechanisms underlying NAFLD-associated NASH progression is critical for developing targeted pharmacological interventions capable of preventing, ameliorating, or potentially reversing disease progression.

Screening in Primary Care of Advanced Liver Fibrosis in NAFLD And/or Alcoholic Patients

The primary objective of the SOPRANO study is to compare two blood fibrosis tests, the eLIFT and the FibroMeter, for the screening of advanced liver fibrosis in patients with NAFLD and/or ALD from primary care centers.

Combined Active Treatment in Type 2 Diabetes with NASH

The aim of this multicentre, prospective, placebo-controlled, double-blind, randomized, 3-arm parallel group, interventional study is to assess for the first time the effects of either a combined therapy with the antihyperglycemic drugs semaglutide and empagliflozin or empagliflozin monotherapy compared to placebo as potential treatments for non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes.

Integrated Phenotyping of the Gut-plAtelet-Liver AXIS in the Progression of Chronic Liver Disease (iGAL-AXIS)

Objective of the study Our working hypothesis is that platelets activated by gut-derived metabolites dock in the liver of NAFLD patients and amplify the inflammatory state by releasing pro-inflammatory cytokines/chemokines, which in turn recruit and activate leukocytes in the liver sinusoids. Combined stimuli from leukocytes and platelets would then lead to metabolic reprogramming of hepatocytes, progression to NASH and eventually cirrhosis. To test this hypothesis, the investigators propose 2 objectives. Primary objective: To identify platelet features that correlate with liver disease progression. Secondary objective: To study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.

Effectiveness of Nutrition Education Program and Omega-3 Supplementation Among Non-alcoholic Fatty Liver Disease Patients

The aim of this clinical trial is to examine the impact of nutritional education and omega-3 supplementation in influencing body weight, liver enzyme levels, and lipid profiles in patients diagnosed with non-alcoholic fatty liver disease. Eligible patients who have non-alcoholic fatty liver disease are randomized to receive either nutritional education, omega-3 fatty acids containing DHA and EPA, or control groups. the main questions are: Does the Nutrition education affect body mass, liver enzyme and lipid profile in patient with non-alcoholic fatty liver disease? Does Omega-3 supplementation affect body mass, liver enzyme and lipid profile in patient with non-alcoholic fatty liver disease? The expected outcome will improvement in the laboratory liver tests, liver steatosis on ultrasound, and lipid profile and also decrease body weight.