Clinical Research Directory

Dynamic Post-Prandial Metabolism in Patients With Non-Alcoholic Fatty Liver Disease

Background: Metabolism refers to the many chemical pathways by which various compounds, including food, are processed and used in the body. People with non-alcoholic fatty liver disease (NAFLD) have too much fat in their liver cells, but what causes it is unclear. One explanation is that people with NAFLD process food and metabolize it differently than people without NAFLD. Researchers want to compare how food is metabolized in people with and without NAFLD. Objective: To better understand how food intake influences the development and progression of NAFLD. Eligibility: People ages 18 and older with NAFLD or with a non-NAFLD metabolic syndrome Healthy volunteers ages 18 and older Design: Participants will be screened with medical history, surveys, physical exam, and blood tests. This will have ultrasound of the abdomen. This uses sound waves to image internal organs. Participants will stay at the Clinical Center for 2 nights. They will fast he first night. On the second day they will: Have their metabolism monitored in a metabolism research room for 24 hours Have a catheter inserted into an arm vein for several blood tests Drink an Ensure Plus for breakfast Have solid meals for lunch and dinner Have several urine tests. The final morning, they will: Have more blood tests. Have a DXA test to measure the fat in the body. They will lie on their backs for 15-25 minutes while an x-ray machine is positioned over areas of the body. ...

Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

Background: * Vitamin E is an antioxidant that reduces the damaging effects of oxygen in the body. Most American men (90%) and women (96%) do not get enough vitamin E from their diets; however, the amount of vitamin E needed by the body has been studied only in men, not women. In addition, it is unknown whether another antioxidant, vitamin C, helps vitamin E in protecting the body. Because vitamin E is a fat-soluble vitamin, how much body fat a person has could affect the amount of vitamin E needed for protection. Objectives: This study has three arms to examine vitamin E requirements: * To determine the amount of fat required to get the best vitamin E absorption from a meal. * To determine the amount (i.e., best dose) of vitamin E that must be consumed before it can be measured in the blood. * To examine how vitamin E and vitamin C work together in the body, in conjunction with diet and vitamin supplements. Eligibility: * Arms 1 and 2: Women between the ages of 18 and 40 years who have a normal weight and body mass index (BMI) of 27 or less. * Arm 3: Women between the ages of 18 and 40 years who have a normal weight (BMI 27), who are overweight (BMI \> 27), or who are overweight (BMI \> 27) and have non insulin-dependent diabetes. Design: * Arm 1: Five studies, each lasting 1 month with 1 month off between studies (total study = 10 months). Participants will take 500 1,000 mg of vitamin C twice daily for 2 weeks before admission to the clinical center for 1 week. * Study 1: Participants will eat breakfast containing a known amount of fat, after which they will take a vitamin E pill as well as receive an IV injection of vitamin E. Other foods contain only negligible amounts of vitamin E. Blood and urine samples will measure levels of vitamin E and other substances. * Studies 2 5: Outpatient visits will consist of the same tests as in Study 1; however, the amount of fat in the breakfast will range from 0% to 40% in random order. During one of the studies, an adipose tissue biopsy will be collected to determine how much vitamin E is in the tissues. * Arm 2: Five studies, each lasting 1 month with 1 month off between studies (total study = 10 months). Preparation for Arm 2 is the same as in Arm 1. The proportion of fat, muscle, and water in the body will also be measured. * Study 1: Participants will eat breakfast containing 30% fat, after which they will take a vitamin E pill as well as receive an IV injection of vitamin E. Conditions and procedures are the same as in Arm 1. * Studies 2 5: Outpatient visits will consist of the same tests as in Study 1; however, the amount of vitamin E in the breakfast will range from 2 to 30 mg in random order. * Arm 3: Outpatient (2 to 6 weeks) and inpatient studies (4 to 6 weeks). * Outpatient study: Participants will take 500 1,000 mg of vitamin C daily and provide blood and urine samples, as well as an adipose tissue sample. * Inpatient studies: Two vitamin E inpatient studies. Before these begin, participants vitamin C blood levels will be reduced by means of a diet low in vitamin C. Blood tests will determine how quickly vitamin C leaves the body. Once the vitamin C level is reduced, the first vitamin E study will begin. Study A: The procedure for this study is the same as in Arm 2, Study 1. Study B: The procedure for this study is the same as in Study A, except that the participants blood vitamin C levels will be higher. ...

Exploratory Analysis of Enhanced Liver Function (ELF) Test to Detect Early Fatty Liver in High Risk Population

In this initial investigator-initiated retrospective study, aim to analyze the enhanced liver fibrosis (ELF) scores in this high-risk population for NAFLD/nonalcoholic steatohepatitis(NASH)-related fibrosis. Study define 'high-risk' to include metabolic syndrome, which can be further defined by an atherosclerotic cardiovascular disease (ASCVD) score \>7.5, any diagnosis of hyperlipidemia, history of coronary artery disease, history of heart failure, hypertension and/or type 2 diabetes. Study would also like to compare the performance of this score with historical methods of fibrosis assessment, where applicable, including vibration-controlled transient elastography, magnetic resonance elastography, blood markers and liver biopsy. Study will assess the impact of ELF scores on predicting liver events in the time, have used it and determine if diet, lifestyle changes and/or pharmacotherapy will improve serial ELF scores. Will also seek to understand how ELF scores are distributed in our community.

Early Tracking of Childhood Health Determinants (ETCHED) Study

Background: Children s weight has increased sharply in recent years. This may put them at higher risk for health problems. High blood glucose in a pregnant mother and too much weight gain during pregnancy also may have long-term effects on the child s health. Children who become overweight or obese during childhood tend to remain so as adults. Researchers want to study many risk factors during and after pregnancy, and how these affect a child s development. They will also follow the mother s health and well-being after pregnancy. Objectives: To learn how a pregnant mother s environment, lifestyle, and health conditions may affect her child s growth and development from birth until adulthood. Eligibility: American Indian/Alaska Native (AI/AN) or Hispanic adult pregnant women and their offspring. Design: Mothers will have 3 visits during pregnancy. In the child s first year, mothers will have 2 visits and their child will have 4. Children will have 2 visits in their second year and 1 each year until they turn 18. Mothers will have a visit 2 years after birth and 4-5 years later. Both the mother and child s medical records will be reviewed. They will have physical exams and give blood and stool samples. Mothers may give cord blood and placenta samples. They will give breastmilk and urine samples. They will fill out questionnaires. They will have an ultrasound. They may get an activity monitor. Mother and child will be followed until the child s 18th birthday.

Impact of Ganoderma Lucidum on NRF2 Levels and Antioxidant Status in Metabolic Asscociated Fatty Liver Disease (GL-MAFLD-NRF2 Study)

This RCT investigates the impact of Ganoderma lucidum on antioxidant staus, NRF2 levels and lipid metabolism in individuals with Metabolic Associated Fatty Liver Disease.

Samsung S-Viscosity vs Canon Dispersion Slope in Steatotic Liver Disease (SAVID-SLD)

Steatotic liver disease (SLD) is one of the most common chronic liver diseases worldwide. Distinguishing simple steatosis from metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis is clinically important, but liver biopsy - the current standard - is invasive. Recent ultrasound technology allows noninvasive measurement of tissue viscoelasticity, which has been linked to liver inflammation. Samsung Medison's HERA W12 system (S-Viscosity) and Canon Aplio i800 (Dispersion Slope Imaging) both provide vendor-specific viscoelasticity parameters derived from shear-wave dispersion analysis, but their relationship and agreement have not been compared in SLD patients. This prospective single-center observational study will enroll approximately 95-100 participants in three cohorts: (A) 15-20 living-donor candidates as a healthy reference, (B+C) approximately 80 adults with sonographically suspected or confirmed SLD recruited consecutively. SLD participants will be classified post-hoc into low-MASH-risk (Cohort B) and at-risk MASH (Cohort C) subgroups using a multi-parametric stratification combining liver stiffness (LSM), DeepUSFF (deep-learning-based ultrasound fat fraction), and serum AST. All participants will undergo same-day ultrasound examination with both Samsung HERA W12 and Canon Aplio i800. The primary objective is to evaluate the correlation and agreement between Samsung S-Viscosity and Canon Dispersion Slope. Secondary objectives include deriving a normal reference range from the healthy cohort, comparing viscoelasticity parameters across cohorts, and exploring a Modified US-FAST score.

Siemens Biomarker Multi-modality

The purpose of this study is to see how well Photon Counting CT (PCCT) and ultrasound test results can find fat and scarring in the liver. They will be compared to MRI test results as the reference standard. Participants will get a regular CT scan on the PCCT scanner, plus a few extra pictures just for the study. They will also get an MRI, either on the same day or a different day, whichever is preferred. Participants will get an ultrasound on the same day as the MRI. If they have not had a hematocrit blood test in the past 24 hours, they will also receive one on the day of the CT scan.

GLP-1 RA on Alcohol Consumption, Metabolism and Liver Parameters in Patients With Obesity and Fatty Liver Disease

There is evidence that alcoholic beverage consumption significantly interacts with food energy intake. Furthermore, there is accumulating evidence showing independent, combined, and modifying effects of alcohol and metabolic factors on the onset and progression of chronic liver disease. Preclinical and clinical data have showed that GLP-1 RA can decrease alcohol consumption, particularly in obese patients. Moreover there is evidence that semaglutide can improve the liver sinusoidal milieu in pre-clinical models of cirrhosis. In this study, the investigators aim to assess if patients treated with semaglutide and receiving counselling will achieve a significantly higher alcohol abstinence compared to patients only receiving counselling.

Personalized Transcranial Magnetic Stimulation (TMS) for Metabolic Dysfunction and Alcohol-Related Liver Disease

The goal of this clinical trial is to learn if repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique, works to treat Metabolic dysfunction-associated and alcohol-associated liver disease (MetALD). The main questions it aims to answer are: * Can rTMS effectively treat MetALD? * Is an individualized, precision-targeted rTMS approach more effective than the standard rTMS method? * What changes in brain activity are associated with the treatment? Researchers will compare three different types of stimulation: * Group A: Individualized rTMS targeting a deep brain reward area (the Nucleus Accumbens) based on each participant's brain scan (fMRI). * Group B: Standard rTMS applied using the traditional "5 cm" rule for positioning. * Group C: Sham (placebo) rTMS, which mimics the procedure but delivers no significant magnetic stimulation. Participants will: * Be randomly assigned to one of the three groups (A, B, or C). * Undergo an MRI brain scan before starting treatment. * Receive a total of 20 rTMS sessions, completing at least 4 sessions per week. * Have additional MRI scans and clinical assessments halfway through and immediately after the treatment course. * Attend follow-up visits at 1, 3, and 6 months after treatment completion to assess long-term effects.

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.

Erdosteine in the Treatment of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a global public health concern, and the leading cause of chronic liver disease, especially in developed countries (1). NAFLD is characterized by lipid accumulation in the liver not attributed to other causes. NAFLD is characterized by excessive hepatic fat accumulation without other recognized causes of increased fat content (e.g., alcohol, virus, drugs, and autoimmunity). According to the Clinical Practice Guidelines of the European Association for the Study of the Liver, the diagnosis of NAFLD requires the exclusion of daily alcohol consumption \>30 g for men and \>20 g for women

Cilostazol in the Treatment of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a global public health concern, and the leading cause of chronic liver disease, especially in developed countries (1). NAFLD is characterized by lipid accumulation in the liver not attributed to other causes. NAFLD is characterized by excessive hepatic fat accumulation without other recognized causes of increased fat content (e.g., alcohol, virus, drugs, and autoimmunity). According to the Clinical Practice Guidelines of the European Association for the Study of the Liver, the diagnosis of NAFLD requires the exclusion of daily alcohol consumption \>30 g for men and \>20 g for women

Study of the Efficacy and Safety of Nicotinamide in Patients With Liver Fibrosis (NICOFIB)

The objective of this clinical trial, a pilot study, is to assess the impact of nicotinamide (NAM) on individuals with hepatic fibrosis. The main question it aims to answer is: \- To determine if the treatment with NAM is able to arrest, or even reduce, the hepatic fibrosis. In addition, we also want to study the effect of NAM on: * General parameters (weight, HOMA-IR, etc). * Adiposity distribution (liver and body). * Systemic inflammation. * Thermogenic capacity of adipose tissue. * Microbiota composition. Researchers will compare NAM to a placebo, to see if NAM can arrest or revert hepatic fibrosis and its associated effects. Participants will take either NAM or placebo. The dosage will be 1.2g/m2 NAM per day, for one year.

Blood Collection Biorepository for Liver Disease Research

The purpose of establishing a biorepository is to provide high quality specimens (serum, plasma, buffy coat and liver tissue) for future researchers who are studying the effects that fatty liver and viral diseases have on the liver.

Evaluation of a New Ultrasound System for the Non-invasive Assessment of Liver Steatosis in MASLD/MASH Patients

The objective of the study is to evaluate an ultraportable ultrasound device, Hepatoscope, for the non-invasive assessment of hepatic steatosis in patients with metabolic-dysfunction associated liver diseases (MASLD), by comparing its measurements with current diagnostic modalities, such as MRI-PDFF.

Gepaktiv vs UDCA and Ademetionine in MAFLD With Hepatomegaly

This study compares the effectiveness of the dietary supplement Gepaktiv with standard medications (UDCA and Ademetionine) in patients with fatty liver disease (MAFLD) and liver enlargement (hepatomegaly). Key points: * Participants will receive either Gepaktiv, UDCA, or Ademetionine for 15 days * Doctors will monitor liver health through blood tests and ultrasound scans * The study will check if Gepaktiv helps improve liver function as effectively as standard treatments. Main measurements: * Changes in liver enzyme levels (ALT, AST) * Reduction in liver size * Improvement in fat accumulation (steatosis) measured by FibroScan This research may provide evidence for a new natural option to support liver health.Data analysis will be done by an independent biostatistics

Development of a Non-invasive Screening Tool to Predict Metabolic Dysfunction-associated Steatotic Liver Disease

A generic screening study to establish structural and/or functional baselines of specific organs.

Pioglitazone and Empagliflozin for Fatty Liver Disease in Type 2 Diabetes

This exploratory study will assess the efficacy of combined pioglitazone and empagliflozin therapy in improving hepatic and metabolic outcomes in patients with type 2 diabetes mellitus and metabolic dysfunction-associated fatty liver disease (MAFLD). Although each agent has shown beneficial effects individually, evidence on their combined impact on liver health is scarce. This study seeks to determine whether the combination therapy yields additive improvements in hepatic steatosis, inflammation, and fibrosis, potentially offering a new therapeutic strategy for diabetic patients with fatty liver disease.

Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis

This is a phase 2 randomized, double-blind, placebo-controlled parallel group study of 3 dose levels of HU6 in subjects with nonalcoholic steatohepatitis (NASH). Six months (26 weeks) of dosing is planned, and subjects will be followed for safety, efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) during this time. The end-of-study visit will take place approximately 4 weeks after the last dose of the study drug (Week 30).

Effect of CoQ10 on the Outcome of MAFLD Patients

So far there has been no universal treatment for MAFLD since it has a complex etiology that involves ethnic, genetic, metabolic and environmental factors. However, therapeutic life changes including: diet, weight loss, and physical activity remain the cornerstone of treatment and is recommended by both American and European associations. Inflammatory biomarkers, such as tumor necrosis factor-alpha, and adipokines play key roles in the pathogenesis of MAFLD, hence, the anti-inflammatory and antioxidant effects of coenzyme Q10 especially at high doses that have not been tested are hypothesized to have a beneficial role in improving the systemic inflammation and biochemical variables. This study is conducted to test this hypothesis

Effects of Compound Probiotics-Polygonatum Sibiricum on Liver Health and Metabolism in Middle-aged and Elderly People

The purpose of this study was to evaluate the regulatory effects of Huangqian-biobacteria compound preparation on liver health and related metabolic disorders in middle-aged and elderly people, observe its effects on liver function indexes, basal metabolic rate, markers of oxidative stress, inflammatory factors and intestinal microecology, and evaluate the incidence of adverse reactions in subjects during the 3-month intervention period.

Cardiac Dysfunction in Patients with Fatty Liver Disease

Cirrhotic cardiomyopathy is seen as a blunted contractile responsiveness to stress, and/or altered diastolic relaxation with electrophysiological abnormalities, in absence of known cardiac disease. Left ventricular diastolic dysfunction (LVDD) is associated with risk of hepatorenal syndrome (HRS) , septic shock. , heart failure in the perioperative period following liver transplantation, and after trans-jugular intrahepatic portosystemic shunt (TIPS) insertion . The echocardiographic E/e' ratio is a predictor of survival in LVDD, with multiple studies, including prospective data from our Centre. The inability of the heart to cope with stress or sepsis induced circulatory failure is a key concept of the increased mortality risk due to LVDD. In view of the metabolic syndrome and diabetes epidemic and an increasing number of patients being diagnosed with non-alcoholic fatty liver disease, there is increased risk of developing cardiac dysfunction due to multiple comorbidities including coronary artery disease, hypertensive heart disease, cirrhotic cardiomyopathy, which are contributors to overall cardiovascular risk of mortality.

Burden Fatty Liver Among Acute Ischemic Cerebral Stroke Patients

1. Assess frequency of hepatic steatosis among patients in patients with Ischemic stroke without previous risk factors 2. Assess outcomes morbidity and mortality ischemic stroke in correlation with hepatic steatosis .

Monitoring Changes in Hepatic Steatosis Using Continuous Controlled Attenuation Parameter

Background: Non-alcoholic fatty liver disease (NAFLD) affects 30% of the Asian adult population and is emerging as one of the important leading causes of liver cancer and cirrhosis. Although a number of biomarkersmany have been developed for the assessment of liver fat and fibrosis, most existing studies were cross-sectional in nature. The role of these biomarkers for monitoring and response assessment remains elusive. At present, magnetic resonance imaging proton density fat fraction (MRI-PDFF) is considered the gold standard to in quantifying liver fat. The MRI-PDFF response, defined as a ≥30% relative reduction in liver fat fraction, has been shown to correlate with improved hepatic inflammation and fibrosis. However, MRI is limited by cost and availability. The cContinuous controlled attenuation parameter (CAPc) measurement by vibration controlled transient elastography is a new technology to quantify liver fat. It is a point-of-care test and has the potential to replace the MRI-PDFF as a monitoring and response biomarker in routine practice. Study plan: This prospective cohort study will include 150 patients with NAFLD who will join a 6-month lifestyle modification programme involving dietary intervention and physical training. This will create a cohort of varying degrees of liver fat reduction. Using MRI-PDFF as the reference standard, we will evaluate the accuracy of a changes in CAPc in reflecting the MRI-PDFF response and remission of NAFLD, with all non-invasive tests performed at screening and Month 6. In addition, we will test the hypothesis that the the change in CAPc is superior to the change of in other steatosis tests results (including the original CAP, abdominal ultrasonography and steatosis scores of fatty liver index, hepatic steatosis index, NAFLD liver fat score and NAFLD ridge score) in predicting the MRI-PDFF response. The area under the receiver-operating characteristics curve of the CAPc response in predicting the MRI-PDFF response will be compared with that of the other steatosis tests using the DeLong test.