Clinical Research Directory

A Randomized Controlled Study Evaluating Bariatric Surgery as a Treatment for Severe NASH With Advanced Liver Fibrosis in Non-severe Obese Patients

The aim of the study is to demonstrate the superiority of bariatric surgery on the disappearance of NASH without worsening of fibrosis in comparison to medical standard treatment in obese patients (35 kg/m² \> BMI ≥ 30 kg/m²) with NASH complicated of advanced fibrosis (F3 and F4 fibrosis grade according to Brunt score).

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.

A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis histological stage F2 or F3

A Randomized, Double-Blind, Placebo Controlled Study to Assess the Efficacy and Safety of SNP-610 for the Treatment of Patients With Non-alcoholic Steatohepatitis

The primary objective of the study is to compare the changes in serum ALT level among patients with non-alcoholic steatohepatitis (NASH) following 3-month treatment of 800 mg SNP-610 or the placebo. The secondary objectives will be to compare the changes in liver fat fraction, other liver function tests, cytokeratin-18 (CK-18) fragment level and adverse event / serious adverse event rates among the interventional and placebo arms.

A Study Evaluating Efruxifermin in Subjects With Compensated Cirrhosis Due to NASH/MASH

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis due to NASH/MASH.

Tocotrienol Against the Progression of End Stage Liver Disease

The purpose of this Phase 2 trial is to validate the outcome observed in a previous trial that oral Tocotrienol (TCT) attenuates the rise in MELD score over time in patients with end stage liver disease / cirrhosis. The study is double blind and participants will be randomized to take 2 capsules of TCT (200mg) or placebo twice a day for 3 years.

Investigating the Link Between Type 2 Immunity and NAFLD in Human Obesity

This study is being done to better understand the relationship between inflammation in adipose tissue (AT), abnormal deposition of fat around the liver and how this affects its appearance and function and ultimately insulin resistance.

Statins for the Treatment of NASH

The purpose of this research study is to determine whether the study drug, atorvastatin (Lipitor®), is safe and effective in improving the features of NASH.

Nonalcoholic Fatty Liver Disease in HIV Database

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated with fat accumulation that ranges from benign, non-progressive liver fat accumulation to severe liver injury, cirrhosis, and liver failure. The spectrum of NAFLD encompasses simple nonalcoholic steatosis (nonalcoholic fatty liver \[NAFL\]) and nonalcoholic steatohepatitis (NASH) in which there is evidence of hepatocellular injury and/or fibrosis. NAFLD is the most common liver disease in adults and the second leading cause for liver transplantation in the U.S. The natural history of NAFLD in the general population has been well described. The NASH Clinical Research Network (NASH CRN) was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to further the understanding of the diagnosis, mechanisms, progression and therapies of NASH. This effort has resulted in numerous seminal studies in the field. However, NASH CRN studies have systematically excluded persons living with HIV (PLWH) , as NAFLD in PLWH was thought to be different from that in the general population due to HIV infection, antiretroviral therapy (ART), concomitant medications and co-infections. This resulted in major knowledge gaps regarding NAFLD in the setting of HIV infection. Thus, the natural history of NAFLD in PLWH is largely unknown. The goal of this ancillary study of NAFLD and NASH in Adults with HIV (HIV NASH CRN), is to conduct a prospective, observational, multicenter study of NAFLD in PLWH (HIV-associated NAFLD).

Hepatic Energy Fluxes in NASH and NAS Patients

Diseases along the nonalcoholic fatty liver disease spectrum, which are tightly coupled to the obesity epidemic, are soon to become the commonest indication for liver transplantation in the United States. Bariatric surgery shows great promise in the treatment of these diseases. The studies proposed herein will be the first to measure in humans the relationships among (i) the liver's ability to burn fat and make glucose, two of its primary functions; (ii) the severity of nonalcoholic fatty liver disease; and (iii) the responses to bariatric surgery. These experiments will support deeper future mechanistic investigations of the metabolic mechanisms underlying nonalcoholic steatohepatitis (NASH) improvement with bariatric surgery. The premise of this study is that deranged hepatic mitochondrial metabolism is a key biomarker and mediator of the nonalcoholic fatty liver disease (NAFLD)/NASH continuum, and the central hypothesis the investigators will test is that preoperative hepatic fat oxidation and glucose production flux parameters differ between low versus high NAFLD activity score (NAS), and response of the liver to bariatric surgery can be predicted by preoperative fluxes.

Non-Invasive Quantification of Liver Health in NASH (N-QUAN)

To evaluate, in patients with suspected NASH referred for liver biopsy, the diagnostic performance of CT1 at discriminating those with NAS≥4 \& F≥2 from those without.

Study to Evaluate Efficacy, Safety and Tolerability of HM15211(Efocipegtrutide) in Subjects

This study is a phase 2 study to Evaluate Efficacy, Safety and Tolerability of HM15211 Treatment for 12 Months in Subjects with Biopsy Confirmed NASH

Novel MRE Technique to Assess a Risk Factor for Liver Cancer

The aim of this proposal is to investigate a novel imaging method to identify patients with non-alcoholic steatohepatitis (NASH) who are at risk for hepatocellular carcinoma (HCC).

The Franciscus Obesity NASH Study

The purpose of this study is to evaluate Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) changes in terms of steatosis and elasticity in patients with morbid obesity 1, 3 and 5 years after bariatric surgery. In addition, genomics, microbiome and metabolomics analyses will be carried out.

Estrogen Administration for the Treatment of NASH in Postmenopausal Women

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic in the United States. Despite this, the treatment options remain limited. Preclinical and preliminary clinical data suggest that estrogen deficiency plays an important role in the pathology of steatosis, inflammation and fibrosis in non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD. Post-menopausal women are a growing population with particularly high risk of NASH due to their lack of estrogen. This study will examine the effect of estradiol on hepatic fibrosis and fat in post-menopausal women with NASH.

Biometabolic Outcomes After Weight Loss Surgery: An Individualized Approach

Variable outcomes after weight loss surgery are likely attributable to complex, poorly understood mechanisms. Due to the significant impact that morbid obesity has on a patient's health, successful management of obesity and its related comorbid medical conditions is important and thus necessitates continued improved therapies for treating obesity. Although the mechanisms of weight loss after surgical intervention are poorly understood, improved understanding of molecular and metabolic changes that occur after weight loss surgery may offer the ability to provide targeted precision therapy for patients with morbid obesity undergoing surgical therapy. In this proposal, the investigators will combine a clinical trial whereby modifications to the gold-standard for weight loss surgery, the gastric bypass, are evaluated while simultaneously measuring molecular and metabolic changes that occur in response to these weight loss procedures. Through creating variable lengths of bypass intestine after gastric bypass, the investigators will be able to determine the effect of malabsorption on clinical outcomes and mechanisms involved in weight loss after gastric bypass. The investigators will also use two control groups. One will be a surgical weight loss control group and consist of patients undergoing a laparoscopic sleeve gastrectomy, a non-intestinal bypass procedure. The other group will consist of patients having non-surgical weight loss therapy. To asses metabolic changes that occur in response to surgical weight therapy and specifically intestinal bypass and malabsorption, the investigators will examine changes in the gut microbiome and plasma gut enteroendocrine hormones. To evaluate molecular pathways that are impacted as a result of gastric bypass and malabsorption, the investigators will measure circulating microRNAs (miRNAs) in the blood. Measurement of miRNAs will provide data on an easily measurable molecular marker for each treatment group. This is a first step in translational exploration of mechanisms of weight loss after surgery by evaluating both clinical and molecular/metabolic outcomes and begin an explorative process towards creating an individualized approach to improving outcomes after weight loss surgery.

Vertical Sleeve Gastrectomy and Lifestyle Modification for the Treatment of Non-Alcoholic Steatohepatitis

Participants meeting study entry criteria are randomized with equal probability to one of two study groups: (1) Lifestyle modification or (2) Vertical Sleeve Gastrectomy (VSG) with Iifestyle modification, followed for 12 months. The primary goal for the trial is to determine if the investigators can recruit, randomize, and retain participants to perform invasive and non-invasive measurements of NASH and fibrosis, deliver lifestyle modification and demonstrate the safety of VSG. The investigators wish to also understand which of these two interventions is more effective in achieving, 12 months after entry into the trial, a reduction in NAS composed of the non-weighted scores: (1) steatosis 0-3 (2) Inflammation 0-3 and (3) ballooning 0-2. Secondary goals include comparing the two treatment groups for changes in other measured outcomes including MRI assessments of intrahepatic triglyceride and liver elasticity and serum markers. As a pilot study, a sample size of 20 in each group should offer significant information as to the difference in NAS score reduction between to two groups and achieve adequate power to distinguish clinically significant changes in the primary and secondary outcome measures. These data support the overarching objective i.e. to provide evidence that a larger, longer-term clinical outcomes trial is feasible. A goal is for a longer term follow up for 5 years to assess the durability of treatment effects and treatment differences.

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.

A Study of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (Symmetry)

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in cirrhotic subjects with biopsy-proven F4 compensated NASH.

Safety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis

This is an open-label, randomized study comparing a monitored ketogenic diet intervention using standard ketogenic diet (SKD) and standard of care (SOC) dietary recommendations for 16 weeks. Subjects enrolled in the standard of care group will receive a voucher to Weight Watchers after study completion.

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.

Namodenoson in the Treatment of Non-Alcoholic Steatohepatitis (NASH)

Subjects with biopsy-proven NASH will be randomly assigned in a 2:1 ratio to oral doses of namodenoson 25 mg every 12 hours or matching placebo every 12 hours for 36 weeks. Subjects will be evaluated regularly for safety, and efficacy biomarkers will be measured at Baseline and Weeks 6, 12, 24, and 36. At Week 36, all subjects will undergo liver biopsy.

Disease Prevention in Clinical Practice Base on Patient Specific Physiology

It is well known that the Type 2 diabetes and vascular disease are preceded by over ten years by metabolic dysfunction and anatomic changes that can be quantified. In order to develop effective preventive strategies and reduce the cost burden to the health care system, recognition of the earliest pathophysiology of Type 2 diabetes and vascular disease is clinically relevant. The interval retrospective evaluation of data from patient records, reflect the effectiveness of the various treatments implemented in clinical practice. Prevalence of "prediabetes" among American adults is estimated to be \~84 million, or one out of three Americans. Over a 5-7 year period approximately one third of these prediabetic individuals will progress to type 2 diabetes. Prediabetes is a heterogenous group comprised of individuals with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased A1c (5.7-6.4%). Although different pathophysiologies are present in individuals with IFG and IGT, their conversion rate to overt type 2 diabetes mellitus (T2DM) is similar. Insulin resistance is a common causal feature of many of the pathophysiologic mechanisms linking macrovascular disease and type 2 diabetes. Because hyperglycemia is the major factor responsible for the development of microvascular complications, it logically follows that prevention of progression of prediabetes to overt diabetes should retard/prevent the development of the microvascular complications. From the measurement of plasma glucose, insulin, and c-peptide levels during the oral glucose tolerance test, one can derive measures of the two core defects responsible for the development of T2DM, i.e. insulin resistance and beta cell dysfunction as well as the degree of dysglycemia. By combining a standard medical evaluation with the evaluation of cardiovascular biomarkers, patients at intermediate risk of vascular disease can be identified. In these patients, carotid intima media thickness (IMT) and carotid plaque evaluation is offered to attempt to clarify risk. The hypothesis of this observational study is that the characterization of the physiology and anatomy of patients at risk of developing type 2 diabetes and/or cardiovascular disease can stratify risk of developing disease and direct treatment strategies tailored to the identified physiologic defect, leading to improvements in the delay or prevention of disease.

A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis

A double-blind placebo controlled randomized Phase 3 study to determine if 80 or 100 mg of MGL-3196 as compared with placebo resolves NASH and/or reduces fibrosis on liver biopsy and prevents progression to cirrhosis and/or advanced liver disease