Active clinical trials for "Fatty Liver"

The purpose of this study is to understand why Hispanics who are overweight have a higher incidence of fatty liver disease.

Excessive fat in the liver is associated with impairments in metabolic health. Reducing the amount of carbohydrates and fat both have been shown to reduce liver fat. However, not only the amount fats and carbohydrates, but also their quality have been shown to influence liver fat. Diets high in saturated fatty acids (SFA) and diets with a high glycemic index (GI) have been shown to increase liver fat content. However, available data from human dietary intervention studies is limited and these studies did not reflect a realistic diet. In the present study a combination of low GI/SFA on the one hand and high GI/SFA on the other hand is used to reflect realistically a healthy and an unhealthy diet as they are actually consumed by the Dutch population. The primary objective of this study is to investigate whether a two-week low compared to high GI/SFA diet reduces liver fat content. In addition, it will be investigated whether a two- week low compared to high GI/SFA diet reduces DNL, lowers the 24-hour glycemic response, lowers hepatic glycogen content, increases hepatic fat oxidation and changes hepatic lipid composition. Furthermore, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon the low and high GI/SFA diets.

This study is designed to investigate the effect of NASH (non-alcoholic steatohepatitis) on the disposition of 99mTechnetium(Tc)-mebrofenin and to relate changes in 99mTc-mebrofenin disposition to differences in the bile acid profile and Fibroscan Fibrosis Score of healthy subjects compared to patients with NASH.

SGLT2 inhibitors have been proven to be effective in several preclinical rodent models of non-alcoholic fatty liver disease (NAFLD). Using a choline deficient diet to recapitulate some of the histological features of human non-alcoholic steatohepatitis (NASH), it was found that 5 weeks of SGLT2 inhibition led to significant reductions in hepatic triglyceride content and improved markers of liver fibrosis. Similarly, 4 weeks of treatment in obese mice led to improved glucose tolerance, reduced hepatic steatosis and reduced markers of liver oxidative stress in a dose dependent manner. These findings corresponded with an improvement in traditional liver function tests including the aminotransferases (ALT and AST). The widely used antidiabetic agent metformin has been shown in rodent models to increase hepatic insulin sensitivity and lower liver fat content which is in contrast to the findings in humans where metformin increases hepatic insulin sensitivity, reduces body weight but does not decrease liver fat content. The reason for the discrepancy between the animal and human studies, with regards to liver fat content remains unclear. The investigators hypothesise the following: SGLT2 Inhibitors have the potential to decrease lipid accumulation in the liver through reduced de novo lipogenesis (DNL) There will be no decrease in endogenous lipid synthesis (DNL) with metformin and thus no change in liver fat content. There are two arms to this study. Arm 1: x10 participants with poorly controlled type 2 Diabetes (T2DM) who have been recommended to start an SGLT2 inhibitor called dapagliflozin will be recruited. Arm 2: x13 participants with insulin resistance who have not yet started any diabetic medication will be recruited and will be prescribed metformin at standard clinical doses. The two arms will run in parallel and all participants will undergo identical investigations before and after 3 months of treatment with either dapagliflozin or metformin. Investigations will include liver magnetic resonance imaging/spectroscopy, fat biopsy, fat microdialysis sampling, two-step hyperinsulinaemic euglycaemic clamp, breath sampling and stable glucose and palmitate isotope infusions. The investigators aim to show that SGLT2 inhibition decreases liver fat whereas we aim to demonstrate why liver fat remains unchanged in humans, treated with metformin. These data will provide the first evidence for the use SGLT2 inhibitors in NAFLD, and will be highly informative for the design of future clinical studies. Moreover, the data gained from the metformin arm of the study will provide the first mechanistic evidence in humans of the effects of metformin on hepatic fatty acid metabolism.

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. The investigator's preliminary data support a detrimental role of androgens, or "male sex hormones" on fatty liver in women but no studies have evaluated whether androgens are associated with liver inflammation and/or scarring from fatty liver (aka NASH). To better understand the mechanism by which androgens might promote NASH and/or metabolic co-factors that contribute to NASH, the investigators are conducting a pilot clinical trial to primarily assess the feasibility of using an androgen blocking medication, spironolactone, in women with NASH. Spironolactone was selected because it is has been commonly prescribed for decades with good safety profile and tolerability to treat symptoms of high androgens, like acne and hirsutism in young women. Though primarily a feasibility-focused study, the investigators also aim to explore the pathways by which blocking testosterone receptors might alter the biologic processes that promote NASH and its associated metabolic co-morbidities in women.

This study is for men and women have been diagnosed with non-alcoholic fatty liver disease (NAFLD) and will consequently participate in the YMCA's Diabetes Prevention Program.

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. New evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiosteatosis. The mechanisms behind cardiac involvement and the progression from NAFLD to NASH are poorly understood but must include altered cardiac and intrahepatic lipid handling. In collaboration with renowned research groups from Oxford, Mayo Clinic and Copenhagen investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in these subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using innovative tracer techniques (11Cpalmitate, 11C acetate, 18FDG glucose PET tracers and TG tracers) in combination with hepatic vein catherisation to study cardiac and liver substrate trafficking, as well as NMR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. Effects of acute exercise will be assessed. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism and to assess the effect of exercise on both hepatic, cardiac and adipose and skeletal muscle lipid and substrate utilisation.

This is a non-randomized, 2-part, open-label, drug-drug interaction (DDI) study to evaluate the effect of concomitant administration of fluconazole or quinidine on the pharmacokinetics and safety of EDP-305 in healthy human volunteers.

To evaluate the safety and tolerability of Nitazoxanide (NTZ) 500mg Twice Daily (BID) after 24 weeks of treatment in patients with NASH induced Stage 2 or Stage 3 fibrosis

This is a Phase 1, open-label, drug-drug interaction (DDI) study of ALT-801 under steady state conditions on concomitantly administered medications in healthy subjects. The study will evaluate the effect of ALT-801 on the pharmacokinetics (PK) of metformin, warfarin, atorvastatin, digoxin, and the combined oral contraceptive (OC) ethinylestradiol/levonorgestrel. The study will be conducted in 3 parts, as described below. Each part will have 2 periods in a fixed sequence, where the first period is without ALT-801 administration and the second is with ALT-801 at steady state.