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De Novo Lipogenesis in Severity of NAFLD

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ClinicalTrials.gov Identifier: NCT03683589
Recruitment Status : Recruiting
First Posted : September 25, 2018
Last Update Posted : March 13, 2019
Sponsor:
Collaborators:
American Society for Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Majid Mufaqam Syed Abdul, University of Missouri-Columbia

Brief Summary:
NAFLD is the most prevalent liver disease in the U.S., and there is a serious need to understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH). Previous studies has shown that elevated de novo lipogenesis (DNL) is the unique, early event distinguishing patients with NAFLD from equally-obese subjects with low IHTG. The purpose of this study is to directly by measure DNL in human liver tissue and comparing it to liver histological scores from patient biopsies.

Condition or disease
Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Bariatric Surgery Candidate Obesity, Morbid

Detailed Description:
The development of nonalcoholic fatty liver disease (NAFLD) progresses from a state of elevated intrahepatic triglycerides (IHTG) to liver inflammation, and ultimately, hepatic apoptosis and fibrosis. NAFLD is the most prevalent liver disease in the U.S., and there is a serious need to understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH). Elevated de novo lipogenesis (DNL) is the unique, early event distinguishing patients with NAFLD from equally-obese participants with low IHTG. DNL is the process of liver synthesis of fatty acids (FAs) from carbohydrate. In humans, studies have shown that DNL significantly predicts the magnitude of IHTG, however, it is unknown whether the pathway plays a role in disease progression. Evidence supporting this concept includes the fact that the primary product of DNL is the saturated FA, palmitate, which in cell culture has been shown to significantly contribute to oxidative stress and inflammation. Recent rodent data show that upregulation of DNL through dietary supplementation of sucrose exacerbated the hepatotoxic effects of excess dietary FAs. A preliminary abstract presented by others at the 2017 Liver Meeting suggested that DNL may not be different between patients with low and high liver fibrosis, although these data were collected using an indirect measure of liver disease. Here, in the present study, the hypothesis will be tested directly by measuring DNL in human liver tissue and comparing it to liver histological scores (NAFLD Activity Score, NAS) from patient samples.

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Contribution of de Novo Lipogenesis in Severity of Nonalcoholic Fatty Liver Disease
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : December 31, 2019


Group/Cohort
Study group

Participants will receive deuterated water for 10 days before undergoing bariatric surgery.

Liver biopsy collected, lipids extracted and DNL measured via GC/MS.




Primary Outcome Measures :
  1. De novo lipogenesis [ Time Frame: Dec 2019 ]
    DNL will be measured directly in the liver biopsies


Secondary Outcome Measures :
  1. Histological scores (NAFLD activity score) [ Time Frame: Dec 2019 ]
    Tissue histology will be performed to obtain NAFLD activity score (NAS). A pathologist, trained in determining the NAS of histological samples, grades them for the quantity of fat present, and the levels of inflammation and fibrosis. A score of 0 is considered completely healthy (devoid of any of these three characteristics), while a score of 8 indicates severe pathology, advanced as far as cirrhosis.

  2. Liver enzymes [ Time Frame: Dec 2019 ]
    AST and ALT will be measured on the day when liver biopsy is collected

  3. FibroScan [ Time Frame: Dec 2019 ]
    Liver fat and fibrosis will also be measured non-invasively via FibroScan TM


Biospecimen Retention:   Samples Without DNA
Plasma samples will be stored in a -80C freezer. Liver samples will be tested immediately and will not be stored.


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Ages Eligible for Study:   22 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
The study includes both obese men and women who are undergoing bariatric surgery
Criteria

Inclusion and exclusion criteria are similar to the criteria set by a larger project (NCT03151798).

Inclusion criteria:

  • Men and women (pre and post-menopausal)
  • Overweight/obese with BMI ≥ 25.9 or ≤ 50.0 kg/m2
  • Characteristics of the metabolic syndrome, pre-diabetes (fasting glucose 100-125 mg/dL or 2h glucose 140-200 mg/dL) or diabetes type II
  • 22-65 years of age
  • use of tobacco products or no use of these products
  • Sedentary, ≤ 60 minutes per week of structured physical activity

Exclusion criteria:

• The following conditions exclude subjects for this project because bariatric surgery would not be performed in these populations. Individuals with acute disease or advanced cardiac, liver, or renal disease, excessive alcohol use, anticoagulation therapy, or any severe co-morbid condition limiting life expectancy < 1 year. Women pregnant or trying to become pregnant.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03683589


Contacts
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Contact: Majid Mufaqam Syed Abdul, MS 5738842014 ms9rf@mail.missouri.edu
Contact: Elizabeht J Parks, PhD 5738825864 parksej@missouri.edu

Locations
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United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65212
Sponsors and Collaborators
University of Missouri-Columbia
American Society for Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Elizabeth J Parks, PhD University of Missouri-Columbia

Publications:
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Responsible Party: Majid Mufaqam Syed Abdul, Doctoral Candidate, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT03683589     History of Changes
Other Study ID Numbers: 2012544
R01DK113701 ( U.S. NIH Grant/Contract )
First Posted: September 25, 2018    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Obesity, Morbid
Obesity
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms