Clinical Research Directory

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 overnight, while participants are asleep and fasting (not eating or drinking other than water) and while consuming a standardized diet of nutritional beverages during the following day. The objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.

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.

Liver-gut Axis Study Through Identification of Liver Disease-specific Microbiome

In this study, we aim to identify gut microbiomes specific to patients with chronic refractory liver disease and to conduct a gut-liver axis study on the pathogenesis and disease progression.

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.

FibroScan-Reproducibility and Repeatability Study

Chronic liver disease (CLD) is a serious health issue worldwide, often progressing without symptoms until advanced stages with risks of complications like liver cancer and cirrhosis. Early detection is crucial to help prevent these outcomes. Liver stiffness measurement (LSM) can detect fibrosis (scarring) in the liver, a common issue in CLD patients while traditional methods like liver biopsy are invasive and not ideal for regular screening and monitoring. FibroScan, a non-invasive device, measures the liver stiffness and fat content in the liver. This study will assess how reliable and consistent FibroScan results are when used by different operators and across different days, focusing on patients with liver conditions like metabolic-related liver disease (MASLD), alcohol-related liver disease (ALD), and hepatitis B. This research also aims to test both the standard and Guided VCTE (Vibration Controlled Transient Elastography) FibroScan generations to evaluate their reproducibility and repeatability. As secondary objectives the Control Attenuation Parameter (CAP) results, and the FAST, Agile 3+, and Agile 4 scores will be evaluated to compare their reproducibility and repeatability. Adult participants will attend two visits within three days. During these visits, they will undergo multiple FibroScan scans that include five scans on Day 1 (visit 1) and four scans on the follow up visit (visit 2), one blood sample for liver health assessment on each visit, and an AUDIT questionnaire on Day 1 (visit 1). Some participants may undergo only two scans on the follow-up visit since this will depend on operator availability. Each session will last 25-45 minutes including all examination types. The study is funded by Echosens, the manufacturer of FibroScan, and will be conducted at UK healthcare facilities in England. By evaluating the variability of FibroScan results, this research could lead to a better understanding of the device's reproducibility and reliability in measuring liver stiffness across different operators and time points, potentially enhancing clinical confidence in its use for managing chronic liver diseases.

Endoscopic Ultrasound Shear Wave Elastography in Patients With Non-alcoholic Fatty Liver Disease

The goal of this observation study is to assess whether endoscopic ultrasound shear wave elastography (EUS-SWE) may be a useful tool for liver fibrosis screening in patients with elevated body mass index and non alcoholic fatty liver disease as compared to other non-invasive screening modalities, which have traditionally had less accurate results in this population. The main questions it aims to answer are: * Determine accuracy of EUS-SWE for liver fibrosis screening compared to other non-invasive scoring systems, such as the FIB-4 score and Fibroscan in patients with elevated body mass index * Establish optimal stiffness (kPa) cutoffs for liver fibrosis grading for EUS-SWE for this patient population in reference to the gold standard liver biopsy, as no standard cutoffs currently exist. Participants will undergo routine endoscopic ultrasound as part of their standard clinical care and indication. Participants are consented for the procedure and undergoing the shear wave elastography. In addition to their standard ultrasound test, it takes on average an extra 2-3 minutes to perform the shear wave elastography. The procedure itself adds no additional risk to the patient and does not expose them to radiation.

Diet and Meal Timing in Patients With Metabolic Dysfunction Associated Steatoic Liver Disease

This study will assess the impact of time-restricted eating (8 hours of eating each day) with standard of care lifestyle recommendations (hypocaloric, Mediterranean diet and 30 minutes of exercise on at least 5 days/week) on the degree of fat in the liver as measured by magnetic resonance imaging.

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.

Comorbidities Resolution After MGB Surgery and Change in Body Composition

This observational study aims to learn about the correlation between the improving comorbidities associated with obesity after MGB (Mini-Gastric Bypass) surgery and changes in body composition in morbidly obese patients. The main questions it aims to answer are: To study the correlation between the improving comorbidities associated with obesity after MGB(Mini-Gastric Bypass) surgery and changes in body composition. Other objectives are: * Changes in the parameters of the metabolic syndrome after surgery * Changes in the cardiovascular risk biomarkers after metabolic surgery * Emergence in complications arising out of surgery requiring any intervention or causing a prolonged hospital stay, or requiring additional outpatient visits. Type of Study: An observational study in which participants with morbid obesity will undergo mini-gastric bypass surgery as per routine protocol. No separate experimental interventions will be done in the study for the participants.

A Randomized, Double-blind, Single-center Phase I/IIa Study of XTYW007 Tablets in Subjects.

Aimed at evaluating the safety, tolerability, and pharmacokinetic characteristics of single and multiple doses of XTYW007 in healthy subjects and healthy subjects with elevated LDL-C, as well as studying the effects of food on the pharmacokinetics and metabolic transformation of XTYW007, and preliminarily assessing the pharmacodynamics of XTYW007.

"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".

Development of preclinical translational models for chronic liver tumors and diseases study, such as spheroids cultured in autologous medium and murine xenograft models to test the efficacy of new therapeutic strategies.

Integrated Diagnostics for Early Diagnosis of Liver Disease

This is an observational study that will explore the hypothesis that by combining data from patients with liver disease with novel blood biomarkers, single nucleotide polymorphism (SNP) analysis and faecal microbiome analysis. The Investigators will improve diagnosis of liver fibrosis compared to the current available diagnostic tools.

Human Models of Selective Insulin Resistance: Pancreatic Clamp

This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the impact of lowering insulin levels on hepatic glucose production (HGP) vs de novo lipogenesis (DNL) in people with insulin resistance. The investigators will recruit participants with a history of overweight/obesity and evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and/or impaired fasting glucose and/or Homeostasis Model Assessment of Insulin Resistance \[HOMA-IR\] score \>=2.73), and with evidence of metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo two pancreatic clamp procedures -- one in which serum insulin levels are maintained near hyperinsulinemic baseline (Maintenance Hyperinsulinemia or "MH" Protocol) and the other in which serum insulin levels are lowered by 50% (Reduction toward Euinsulinemia or "RE" Protocol). In both clamps the investigators will use stable-isotope tracers to monitor hepatic glucose and triglyceride metabolism. The primary outcome will be the impact of steady-state clamp insulinemia on HGP vs DNL.

MN-001 in Non-alcoholic Fatty Liver Disease, Type 2 Diabetes Mellitus, and Hypertriglyceridemia

The design of the Phase 2 clinical trial includes the following elements: * Multi-center, two-arm, randomized, double-blind, placebo-controlled trial to evaluate MN-001 (tipelukast) vs. placebo in approximately 40 patients in the U.S. * Patients will be randomized 1:1 to receive either 500 mg/day of MN-001 (tipelukast) or placebo for 24 weeks. * The co-primary endpoints are (1) change from baseline in liver fat content measured by controlled attenuation parameter (CAP) score at Week 24, and (2) change from baseline in fasting serum triglycerides at Week 24. FibroScan® is a non-invasive, quantitative, and accurate measure of liver fat content commonly used in early phase trials to measure treatment response. * Secondary endpoints include safety and tolerability and changes in lipid profile (HDL-C, LDL-C, and total cholesterol).

Mechanisms of SGLT2 Inhibition in Pediatric Steatotic Liver Disease

This study is a randomized, double-blind, placebo-controlled trial specifically designed to evaluate the preliminary feasibility, initial efficacy and safety of SGLT2 inhibitors for treating NAFLD in adolescents with obesity.

SGLT2 Inhibitors as a Novel Treatment for Pediatric Non-Alcoholic Fatty Liver Disease

This study is a randomized, double-blind, placebo-controlled trial specifically designed to evaluate the preliminary feasibility, initial efficacy and safety of SGLT2 inhibitors for treating NAFLD in adolescents with obesity.

The Olmsted NAFLD Epidemiology Study (TONES)

Researchers are assessing the prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) in the population and assembling a well-characterized cohort of adults with NAFLD and NASH to validate models of NAFLD diagnosis and determine long-term outcomes.

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

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.

Intermittent Fasting for NAFLD in Adults

NAFLD is a growing threat to public health. Currently, there is a significant need for highly effective treatments for NAFLD. Non-obese NAFLD (BMI\<30kg/m2) is an increasingly recognized condition, sometimes described as "lean NAFLD". Intermittent Fasting (IF) may be uniquely beneficial in non-obese NAFLD. The purpose of this study is to identify non-pharmacologic, lifestyle-based methods of NAFLD treatment within non-obese adults.

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.

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.

Screening for NAFLD in Flanders

In the Belgian adult population more than half, and numbers are still increasing, of the population is overweight or obese. These people are at risk to develop NAFLD. However, we lack epidemiological data in Belgium. Therefore, it is important to do epidemiological studies to investigate NAFLD prevalence and disease severity based on a non-invasive approach and evaluate how patients are to be referred.

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. ...