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

Fatty Liver Clinical Trial

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

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder in the Western world and is a leading cause of liver-related morbidity and mortality. Excessive caloric intake and specific nutritional components have been implicated in its pathogenesis, but the complex metabolic pathways linking nutrient consumption with hepatic fat accumulation have not yet been fully elucidated. Analysis of pathophysiology and the search for biomarkers in NAFLD has largely focused on fasting samples; the dynamic response to a caloric load has not been interrogated, beyond glucose tolerance testing. Metabolomics is a novel high-throughput technique, allowing for simultaneous detection of hundreds to thousands of metabolites, and the evaluation of their interconnectivity and causal relationships. We propose a pilot study to investigate the metabolic response of patients with NAFLD to a standardized food challenge, by applying a metabolomics-based dynamic approach. In this study we will recruit up to 50 patients with NAFLD and compare them to 12 controls with metabolic syndrome without NAFLD, and 12 healthy controls. Following an overnight fast, subjects will be situated in a metabolic chamber for continuous measurement of metabolic rates and will be given a liquid mixed meal containing approximately 30% of daily caloric requirement over a period of 15 minutes. The energy expenditure (EE) and respiratory quotient (RQ), reflecting preference for carbohydrate or fat oxidation, will be measured at 1-minute resolution. Blood will be drawn at baseline, and at 30 min, 1, 2, 4 and 24 hours after ingestion. Plasma will be separated and stored in -80 (Infinite)C. Following completion of recruitment, stored samples will be analyzed at the NCI Laboratory of Metabolism by LC/MS and GC/MS, metabolites of interest identified, and individual metabolites quantitated and normalized to their pre-prandial level. Study results will hopefully identify novel metabolic markers of disease, and uncover altered signaling pathways unique to NAFLD that are activated primarily under fed state conditions. ;

Related Conditions & MeSH terms

• Fatty Liver
• Liver Disease
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

• NCT number: NCT02520609
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Start date: October 28, 2015
• Completion date: May 14, 2020