Clinical trial NCT01807910: ER Stress in NAFLD
Official title: Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Obesity
NAFLD
Keywords: Obesity
NAFLD
NASH
Steatosis
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2013-03-08
Enrollment: 0
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Net hepatic phospholipid production
timeFrame: Baseline and 2 weeks
Secondary outcomes:
measure: Kinetics of secretory lipoprotein phospholipids
timeFrame: Baseline and 2 weeks
Other outcomes:
measure: Changes in zonation of phospholipids and PEMT in liver tissues
timeFrame: 60 months
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Charles R Flynn, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Naji N Abumrad, MD
role: STUDY_CHAIR
References: