Clinical Research Directory

MASLD in Primary Hypothyroidism and Efficacy of Dapaglifozin

Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25-40%.Primary Hypothyroidism is one of Endocrinopathies who are at risk of developing NAFLD/NASH and estimated prevalence of Primary Hypothyroidism in NAFLD patients is 10-15 %.Though First line Management is Dietary changes and lifestyle modifications(LSM),unfortunately Adherence to Lifestyle has been poor,rise of Lean NAFLD is on rise, faster progression of NAFLD,evolving risk factors for NAFLD like endocrinopathies,these push need for Pharmacotherapy.Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors can reduce hepatic fat content in patients with DM which is independent of glycemic control. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated.Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is an emerging non-invasive imaging technique, and is more sensitive than liver biopsy/histology in quantifying liver fat change. Liver stiffness measurement (LSM) by Transient Elastography is a non-invasive method to diagnose fibrosis/cirrhosis with high accuracy.The novelty of utilizing the concept of "drug repositioning" by changing the role of SGLT2 inhibitors in treating DM to treating NAFLD in patients without DM deserves exploration.The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of Dapagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients with Primary Hypothyroidism.The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis/hepatic fibrosis in NAFLD patients with Primary Hypothyroidism.

Human Models of Selective Insulin Resistance: Alpelisib, Part I

The goal of this clinical trial is to understand how the blood sugar-lowering hormone insulin works in healthy adults versus those who are at risk for type 2 diabetes. The study will use a drug called alpelisib, which interferes with insulin's actions in the body, to answer the study's main question: does the liver continue to respond to insulin's stimulation of fat production even when it loses the ability to stop making glucose (sugar) in response to insulin. Researchers will compare the impact of single doses of both alpelisib and placebo (inert non-drug) in random order (like flipping a coin) in study participants. Participants will be asked to stay twice overnight in the hospital, take single doses of alpelisib and placebo (one or the other on each of the two hospital stays), and receive intravenous (into the vein) infusions of non-radioactive "tracer" molecules that allow researchers to measure the production of glucose (sugar) and fats by the liver. Measurements will be done both while participants are fasting (not eating or drinking other than water) and while consuming a standardized diet of nutritional beverages. The objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.

Impact of Lifestyle Interventions on Cognitive Decline in Non-alcoholic Fatty Liver Disease

This study investigates whether a structured lifestyle program can help improve thinking skills and liver health in adults with Non-Alcoholic Fatty Liver Disease (NAFLD). We are enrolling 45 participants, aged 18-42, who will be randomly assigned to one of three groups for six months: one receiving general health advice, a second following a supervised Mediterranean diet plan, and a third combining the same diet with a regular walking program. The main goal is to see if these diet and exercise interventions can lead to better scores on memory and reasoning tests, reduce liver stiffness measured by a painless scan (FibroScan), and improve related blood markers of inflammation and hormone balance.

InAdvance: Surveillance, Prevention, and Interception in a Population at Risk for Cancer

This research study is creating a way to collect and store specimens and information from participants who may be at an increased risk of developing cancer, or has been diagnosed with an early phase of a cancer or a family member who has a family member with a precursor condition for cancer. * The objective of this study is to identify exposures as well as clinical, molecular, and pathological changes that can be used to predict early development of cancer, malignant transformation, and risks of progression to symptomatic cancer that can ultimately be fatal. * The ultimate goal is to identify novel markers of early detection and risk stratification to drive potential therapeutic approaches to intercept progression to cancer.

Quantifying Hepatic Mitochondrial Fluxes in Humans

In this study the investigators will quantitate hepatic mitochondrial fluxes in T2D patients with NAFL and NASH before and after 16-weeks treatment with the insulin sensitizer pioglitazone

Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)

Background: In non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help. Objective: To find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide. Eligibility: People with NAFLD and healthy volunteers ages 18 and older Design: Participants will be screened with: Medical history Physical exam Blood tests Imaging: A machine will take pictures of the participant s body. Within 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes: Blood, urine, heart, and imaging tests For NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue. Participants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times. The baseline visit concludes participation for healthy volunteers but NAFLD participants will contine. About 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection. Participants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests. Participants will inject semaglutide once a week at home. At week 30, participants will stay in the clinic again and repeat the tests. Participants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests. ...

Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity (ATM)

The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals. Both groups will have: * screening visit * imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging \[MRI\] and magnetic resonance spectroscopy \[MRS\] scans) * Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies

Fibrosis Lessens After Metabolic Surgery

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment. Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.

Nonalcoholic Steatohepatitis in Chinese Children

Nonalcoholic steatohepatitis (NASH) is now recognised as an increasing clinical problem in children. Steatosis without significant liver cell injury or fibrosis is the most common form of nonalcoholic fatty liver disease (NAFLD) in both adults and children. Studies in the adult population have variably suggested that steatosis is a benign nonprogressive condition and NASH is recognised as a potentially serious condition with significantly risk of morbidity and mortality. A growing body of evidence suggests that children with NASH frequently show histopathological features that differ from those of adults. The prevalence of this pattern in a wide range of paediatric cases as well as other histopathological lesions and their relevance and prognostic significance in children with NAFLD remains to be determined. Thus the investigators would like to conduct a study of biopsies and clinical information to document the histological features of paediatric NAFLD, to explore the natural history of paediatric NAFLD, and to determine the frequency and prognostic value of these features.

Moderately Carbohydrate-restricted Diet to Treat NAFLD in Adolescents

This will be a 6-month randomized clinical trial with two arms: moderately carbohydrate-restricted diet and a fat-restricted control diet. This 6-month study will have 2 phases: a 12-week controlled feeding phase and a 12-week "free living" phase. During the controlled feeding phase, all food will be provided to the families of the participants for the entirety of the 12 weeks. Participants (n=80) will have been diagnosed with NAFLD based on the presence of current evidence of active disease, which will be determined by the ongoing presence of hepatic steatosis estimated by diffusely echogenic liver via ultrasound suggestive of fatty liver and a serum alanine aminotransferase (ALT) level of 45 U/L or greater. All participants will be children and adolescents age 10-17 yrs.; will have an HbA1c \<7.0; and will be overweight or obese (BMI \>85th percentile). It is anticipated that most participants will be sedentary. The investigators will inquire as to routine physical activity at screening. All participants will be asked to maintain their usual level of physical activity throughout the study. Physical activity will be monitored via a smart watch provided to each participant at the beginning of the study, and participants will be queried weekly by the study dietitian regarding changes in physical activity. Participants who use oral contraceptives will be asked to maintain consistent use of these preparations throughout the study. Hormone use will be examined as a potential covariate in statistical analyses.

Accuracy of Imaging Techniques in Diagnosing Steatohepatitis and Fibrosis in NAFLD Patients

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition, and when fatty liver is associated with inflammation and hepatocellular injury (steatohepatitis), it can lead to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. Liver biopsy is the gold standard for NAFLD assessment but has several drawbacks. Several drugs for NASH are now in phase 2-3 trials, and if medical treatments become available, non-invasive tools to identify patients who may benefit from a therapeutic intervention will be strongly needed. Some imaging methods have shown promising potential in fibrosis and NASH diagnosis. This study aims to evaluate the diagnostic accuracy of non-invasive imaging methods, including ultrasound (US) and Magnetic Resonance (MR) techniques, in diagnosing NASH and fibrosis in patients with or at high risk of NAFLD, using liver biopsy as the reference standard. Consecutive patients with a clinical indication for liver biopsy assessment of NAFLD are enrolled in this non-inferiority study. They undergo both a liver US and a multiparametric unenhanced liver MR examination. As reference standard, histological diagnosis of fibrosis and steatohepatitis made according to the fatty liver inhibition of progression (FLIP) algorithm is used. Sensitivity and specificity of imaging parameters alone or in different combinations will be calculated with the aim of finding one or more tests with at least 90% sensitivity/specificity compared to liver biopsy.

Effect of Omega-3 PUFA Supplementation in NAFLD Patients

The purpose of this study is to determine whether dietary supplementation with omega-3 polyunsaturated fatty acids will decrease the amount of fat in liver.

Iron Depletion Therapy for Type 2 DM and NAFLD

The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.

Molecular Characterization of Autoimmune Hepatitis: A Lipidomic Approach

This is a two-arm, prospective, controlled observational pilot clinical study aimed at characterizing the lipidomic profile and extracellular vesicles (EVs) of patients with autoimmune hepatitis (AIH) compared to patients with non-alcoholic fatty liver disease (NAFLD). A total of 24 adult outpatients will be enrolled at the Hepatology Outpatient Unit of IRCCS "S. de Bellis". Blood samples will be collected by venipuncture to perform lipidomic analyses on red blood cell membranes and serum, and to isolate and characterize EVs. No intervention beyond standard clinical practice will be applied

Effect of Insulin Lowering on Lipogenesis

The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology. Participants will: * Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose \[mpk\]) or another 14 doses of placebo, over 7 days * Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice * Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study * Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period * Consume their total calculated daily caloric needs as divided into three meals per day Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.

NAFLD in Adolescents and Young Adults With PCOS

This project focuses on an at-risk adolescent and young adult population who may gain long-term health benefits from detection of risk factors at a young age. The primary aims of this proposal are: 1) To observe whether adolescents and young adults with Polycystic Ovary Syndrome (PCOS) are more likely to have elevated liver fat (\>/=4.8%) than controls by studying liver fat deposition measured by magnetic resonance spectroscopy (MRS); 2) To assess the association of percentage liver fat with biomarkers of Non-alcoholic fatty liver disease (NAFLD), dyslipidemia, insulin resistance and body composition in PCOS and controls. In the proposed study, 40 adolescents and young adults with PCOS and 40 age-comparable control subjects will be evaluated for metabolic disturbances and elevated liver fat using noninvasive and state-of-the-art techniques including MRI, dual-energy x-ray absorptiometry and an oral glucose tolerance test in order to fully assess the metabolic and body composition differences between these groups. This research proposal represents a critical step in understanding the metabolic and cardiovascular comorbidities of PCOS and their relationship to NAFLD. The investigator hopes to use the results generated by this research proposal in order to lay the groundwork for the prevention and treatment of metabolic disorders in adolescents with PCOS. The overarching goal is to decrease and prevent lifelong morbidity associated with this common disorder.

Probiotic Lysate (Postbiotic and Metabiotic) Supplementation for Adults NAFLD Patients (DELI_NAFLD Study)

The current study aim was to conduct placebo-controlled randomize clinical trial to assess the short-term efficacy and safety of postbiotics on hepatic fat content as measured by MRI-PDFF and ultrasonography, liver stiffness (LS) measured by Shear Wave Elastography (SWE) and anthropomorphic variables in NAFLD patients. The study will include 3 periods. Screening period of up to 1 weeks to assess the eligibility to inclusion/exclusion criteria. Treatment period for 3 month where the participants will receive a twice daily oral dose of postbiotics (cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023) at the assigned dose of 100mg or placebo in capsules. During this period monthly phone contacts will be done for assessment of compliance and safety concerns. Follow-up period of up to 3 month.

Effect of Endoscopic Sleeve Gastroplasty in Patients With Obesity and MASH: A Randomized Controlled Trial

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals

The investigators recently demonstrated a increase in liver fat in early middle-aged LBW compared to normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). Here the investigators will further examine the Increased risk of non-alcoholic fatty liver disease in low birth weight individuals by performing a validation study.

Investigating Pathological Mechanisms in Non-alcoholic Fatty Liver Disease

To identify key characteristics of the tissue resident and peripherally circulating immune-phenotype in addition to blood markers, metabolic profile, faecal and oral microbiota in non-alcoholic fatty liver disease

Prevention of NAFLD in Hispanic Children

This is a 2 year clinical trial testing an intensive intervention to reduce dietary sugars as a means to prevent non-alcoholic fatty liver disease (NAFLD) in pre-pubertal Hispanic children.

Improving Diagnostic Safety Through STeatosis Identification, Risk Stratification, and Referral in the ED

Hepatic steatosis is a common radiographic "incidental finding" that is overlooked and underreported to patients. The investigators developed a clinical decision support system using machine learning and natural language processing that will prompt reporting to patients and provide ED clinicians risk stratified follow-up care recommendations. Data on both the implementation and effectiveness of our intervention resulting from this trial will inform future use with a goal of ultimately improving diagnostic safety and outcomes for patients with hepatic steatosis.

A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)

A 52-Week, Multi-center, Open-label, Active Treatment Extension Study to Evaluate Safety and Tolerability of Once Daily, Oral Administration of Resmetirom (MGL-3196)

Identification of Liver Fibrosis Biomarkers

Chronic liver disease (CLD) is a major cause of global mortality and morbidity . CLD patients are at an increased risk of developing liver fibrosis (formation of scar tissue), cirrhosis and liver failure and are at significant risk to develop primary liver cancer. Non-alcoholic fatty liver disease (NAFLD) represents a major risk for CLD and it is becoming the most common chronic liver condition with an estimated 25% global prevalence. Progression to non-alcoholic steatohepatitis (NASH) occurs in approx. 1 of 5 NAFLD patients and due to the rapidly rising etiology of end-stage liver disease, is currently the second most common etiology of hepatocellular carcinoma (HCC) requiring liver transplantation. Liver biopsy, currently the gold-standard for grading disease activity and staging fibrosis, is invasive, costly and at risk for sampling error. Due to the number of patients diagnosed with fibrosis and since fibrosis stage is prognostic of mortality and drives patient management, it is important to develop noninvasive yet accurate diagnostic tools that can identify fibrosis stage. The purpose of this study is to obtain a panel of clinically well characterized blood specimens to identify novel biomarkers to be used as an aid in diagnosis to assess the stage of clinically significant hepatic fibrosis in patients with signs or symptoms of NAFLD (NAFL/NASH). In addition, quantitative ultrasound (QUS) based approaches combined with artificial intelligence (AI) algorithms will be explored for assessing the stage of fibrosis.