ER Stress in NAFLD

Early Phase 1WithdrawnNCT01807910

Vanderbilt University

Overview

The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. The investigators plan to examine this hypothesis in a well-characterized cohort of obese subjects that are scheduled for bariatric surgery. Methyl-D9-choline chloride will be infused before and after a 2-week high fructose or glucose feeding to determine the biosynthesis and kinetics of secretory lipoprotein phospholipids. It is proposed that phospholipid metabolism play an important role in the pathogenesis or etiology of fatty liver in non-alcoholic conditions through mechanisms that invoke ER and oxidative stress responses.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Conditions

Obesity NAFLD

Interventions

methyl-D9-cholineDRUG

Subjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids.

Eligibility

Sex: FEMALEMin age: 30 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Ambulatory females age 30-60 years old * Women of all ethnic groups * BMI≥35 kg/m2 * Approval for Roux-en-Y gastric bypass or sleeve gastrectomy. Exclusion Criteria: * Smoking \>7 cigarettes per day * Previous malabsorptive or restrictive intestinal surgery * Pregnant or breastfeeding * Recent history of neoplasia (\<5 years ago) * Malabsorptive syndromes * Inflammatory intestinal disease * Patients with established organ dysfunction * Diagnosis of type 1 or type 2 diabetes mellitus or current use of anti-diabetic medication (last 30 days; last 60days for thiazolidinediones) * Diagnosed hyperbetalipoproteinemia or hypobetalipoproteinemia * Patients on cholesterol lowering medicines * Vegan diet * Hepatic fat content \<10% by MRI * Inability to comply with study protocol such as unable to make study visits or be available daily for phone contact * Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, chronic back pain limiting ability to lay flat, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning.

Locations (1)

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Net hepatic phospholipid production

Net hepatic phospholipid production will be determined using \[11C\]choline dynamic Positron Emission Tomography (PET) before and after high fructose feeding for two weeks. A similar group of control obese subjects will undergo the same procedures before and after two weeks isocaloric glucose feeding.

Time frame: Baseline and 2 weeks

Secondary Outcomes

Kinetics of secretory lipoprotein phospholipids

The biosynthesis and kinetics of secretory lipoprotein phospholipids will be determined using methyl-D9-choline chloride infusion before and after high fructose (or glucose) feeding.

Time frame: Baseline and 2 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.