ER Stress in NAFLD

Vanderbilt University

Status and phase

Withdrawn

Early Phase 1

Conditions

Obesity

NAFLD

Treatments

Drug: methyl-D9-choline

Study type

Interventional

Funder types

Other

Identifiers

NCT01807910

ER stress

Details and patient eligibility

About

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.

Sex

Female

Ages

30 to 60 years old

Volunteers

No Healthy Volunteers

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.