Liver Health and Metabolic Function in People With Obesity
Primary Purpose
Non-Alcoholic Fatty Liver Disease
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Weight loss surgery
Sponsored by
About this trial
This is an interventional diagnostic trial for Non-Alcoholic Fatty Liver Disease
Eligibility Criteria
Inclusion Criteria:
- Body mass index ≥35 kg/m2
- Scheduled for Bariatric surgery
Exclusion Criteria:
- Significant organ disfunction/disease
- Tobacco use
- Previous bariatric surgery
- Pregnancy
- Excessive alcohol use
- Liver disease other than NAFLD
Sites / Locations
- Washington University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Weight loss
Arm Description
Participants will undergo weight loss surgery
Outcomes
Primary Outcome Measures
Hepatic Fibrogenesis
Rates of liver collagen synthesis
Liver histology
Analysis of liver tissue morphology
Secondary Outcome Measures
Plasma protein synthesis
Synthesis rates of collagen-related proteins in plasma
Tissue inflammation
adipose tissue and blood immune cell content
Systemic inflammation
Plasma cytokine concentrations
Tissue bacterial contamination
bacterial 16s ribosomal ribonucleic acid content will be assessed in blood and tissue samples
Body composition
Body composition assessed by dual-energy x-ray absorptiometry and magnetic resonance scans
Intestinal permeability
Urinary excretion of indigestible sugars will be assessed over 24 hours after an oral challenge
Adipose histology
Assessment of adipose tissue morphology
Tissue gene expression
Messenger ribonucleic acid content of adipose, liver and blood tissues will be assessed
Tissue lipidomics
bioactive lipid content of adipose, liver and blood tissues will be assessed
Insulin sensitivity
Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
tissue extracellular vesicles
amount, content and function of extracellular vesicles obtained from adipose, liver, and blood tissue
Liver extracellular vesicles
amount, content and function of extracellular vesicles obtained from liver tissue
adipose tissue progenitor cells
content and function of progenitor cells obtained from adipose tissue
Liver single cell RNA seq
gene expression of liver immune cell types
Liver flow cytometry
liver immune cell content
Full Information
NCT ID
NCT03701828
First Posted
September 10, 2018
Last Updated
August 2, 2023
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT03701828
Brief Title
Liver Health and Metabolic Function in People With Obesity
Official Title
Liver Health and Metabolic Function in People With Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This project aims to determine the effect of significant weight loss on rates on hepatic fibrogenesis in people with obesity.
Detailed Description
Non-alcoholic fatty liver disease (NAFLD) affects approximately 70% of those with obesity and if left untreated can progress to cirrhosis and liver failure. NAFLD stages progress from the stage of simple steatosis to steatohepatitis, and fibrosis The stage of NAFLD is currently best determined using histology from a liver biopsy, however this provides a static depiction of the state of the liver. Therefore This project aims to determine fibrogenesis in the liver of obese humans in vivo, before and after weight loss.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Weight loss
Arm Type
Experimental
Arm Description
Participants will undergo weight loss surgery
Intervention Type
Procedure
Intervention Name(s)
Weight loss surgery
Other Intervention Name(s)
Sleeve gastrectomy, Roux-en-Y, biliopancreatic diversion
Intervention Description
All surgery types will be included. However, only participants scheduled for surgery with collaborating surgeons will be included. Surgery is not provided by study team.
Primary Outcome Measure Information:
Title
Hepatic Fibrogenesis
Description
Rates of liver collagen synthesis
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Liver histology
Description
Analysis of liver tissue morphology
Time Frame
Before and after ~20% weightloss, up to 6 months
Secondary Outcome Measure Information:
Title
Plasma protein synthesis
Description
Synthesis rates of collagen-related proteins in plasma
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Tissue inflammation
Description
adipose tissue and blood immune cell content
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Systemic inflammation
Description
Plasma cytokine concentrations
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Tissue bacterial contamination
Description
bacterial 16s ribosomal ribonucleic acid content will be assessed in blood and tissue samples
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Body composition
Description
Body composition assessed by dual-energy x-ray absorptiometry and magnetic resonance scans
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Intestinal permeability
Description
Urinary excretion of indigestible sugars will be assessed over 24 hours after an oral challenge
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Adipose histology
Description
Assessment of adipose tissue morphology
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Tissue gene expression
Description
Messenger ribonucleic acid content of adipose, liver and blood tissues will be assessed
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Tissue lipidomics
Description
bioactive lipid content of adipose, liver and blood tissues will be assessed
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Insulin sensitivity
Description
Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
tissue extracellular vesicles
Description
amount, content and function of extracellular vesicles obtained from adipose, liver, and blood tissue
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Liver extracellular vesicles
Description
amount, content and function of extracellular vesicles obtained from liver tissue
Time Frame
at the time of surgery only
Title
adipose tissue progenitor cells
Description
content and function of progenitor cells obtained from adipose tissue
Time Frame
Before and after ~20% weightloss, up to 6 months
Title
Liver single cell RNA seq
Description
gene expression of liver immune cell types
Time Frame
at the time of surgery only
Title
Liver flow cytometry
Description
liver immune cell content
Time Frame
at the time of surgery only
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Body mass index ≥35 kg/m2
Scheduled for Bariatric surgery
Exclusion Criteria:
Significant organ disfunction/disease
Tobacco use
Previous bariatric surgery
Pregnancy
Excessive alcohol use
Liver disease other than NAFLD
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Coordinator
Phone
314-362-8250
Email
bhenk@wustl.edu
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Coordinator
Phone
314-362-8250
Email
bhenk@wustl.edu
First Name & Middle Initial & Last Name & Degree
Joseph Beals
Phone
3143628199
Email
bealsjw@wustl.edu
12. IPD Sharing Statement
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Liver Health and Metabolic Function in People With Obesity
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