Back to resultsER Stress in NAFLD
Primary Purpose
Obesity, NAFLD
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
methyl-D9-choline
Sponsored by
About this trial
This is an interventional basic science trial for Obesity focused on measuring Obesity, NAFLD, NASH, Steatosis
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.
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fructose
Glucose
Arm Description
Participants will receive fructose (3g/kg/day) for 2 weeks.
Participants will receive glucose (3g/kg/day) for 2 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01807910
Brief Title
ER Stress in NAFLD
Official Title
Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Withdrawn
Why Stopped
The study was not funded
Study Start Date
October 2013 (undefined)
Primary Completion Date
October 2017 (Anticipated)
Study Completion Date
April 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, NAFLD
Keywords
Obesity, NAFLD, NASH, Steatosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fructose
Arm Type
Experimental
Arm Description
Participants will receive fructose (3g/kg/day) for 2 weeks.
Arm Title
Glucose
Arm Type
Active Comparator
Arm Description
Participants will receive glucose (3g/kg/day) for 2 weeks.
Intervention Type
Drug
Intervention Name(s)
methyl-D9-choline
Intervention Description
Subjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids.
Primary Outcome Measure Information:
Title
Net hepatic phospholipid production
Description
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 Outcome Measure Information:
Title
Kinetics of secretory lipoprotein phospholipids
Description
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
Other Pre-specified Outcome Measures:
Title
Changes in zonation of phospholipids and PEMT in liver tissues
Description
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.
Time Frame
60 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles R Flynn, PhD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Naji N Abumrad, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
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ER Stress in NAFLD
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