ER Stress in NAFLD

Obesity Clinical Trial

Official title:

Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01807910
• Other study ID #: ER stress
• Status: Withdrawn
• Phase: Phase 0
• First received: March 5, 2013
• Last updated: October 22, 2013
• Start date: October 2013
• Est. completion date: April 2018

Study information

• Verified date: October 2013
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• NAFLD
• Obesity

Intervention

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

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in zonation of phospholipids and PEMT in liver tissues	Changes in zonation of phospholipids and PEMT in liver tissues acquired from the same subjects intraoperatively during bariatric surgery will be assessed using MALDI-IMS.	60 months	No
Primary	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.	Baseline and 2 weeks	No
Secondary	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.	Baseline and 2 weeks	No