Nonalcoholic Fatty Liver DiseaseNCT03683589
De Novo Lipogenesis in Severity of NAFLD
An observational study of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by University of Missouri-Columbia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 22 to 65 years
- Conditions the study is for
- Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Bariatric Surgery Candidate
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2019to 31 Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study includes both obese men and women who are undergoing bariatric surgery
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Contribution of De Novo Lipogenesis in Severity of Nonalcoholic Fatty Liver Disease
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.
Read the 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.
- Conditions
- Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Bariatric Surgery Candidate, Obesity, Morbid
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity, Morbid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
De novo lipogenesis
DNL will be measured directly in the liver biopsies
Measured: Dec 2019
Secondary outcomes (3)
Histological scores (NAFLD activity score)
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.
Measured: Dec 2019
Liver enzymes
AST and ALT will be measured on the day when liver biopsy is collected
Measured: Dec 2019
FibroScan
Liver fat and fibrosis will also be measured non-invasively via FibroScan TM
Measured: Dec 2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2018
- Study start1 Feb 2019
- Primary completion21 Aug 2019
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of Missouri-ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- American Society for Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Elizabeth Jane Parks, University of Missouri-Columbia
- Investigators
- Elizabeth J Parks, PhD, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03683589
- Sponsor's protocol ID
- 2012544
- Other IDs
- R01DK113701
- Status last verified
- Oct 2020
- First submitted
- 20 Sep 2018
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014 Mar;146(3):726-35. doi: 10.1053/j.gastro.2013.11.049. Epub 2013 Dec 4.
PubMed 24316260Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005 May;115(5):1343-51. doi: 10.1172/JCI23621.
PubMed 15864352Syed-Abdul MM, Moore MP, Wheeler AA, Ganga RR, Diaz-Arias A, Petroski GF, Rector RS, Ibdah JA, Parks EJ. Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease. J Nutr. 2023 Dec;153(12):3418-3429. doi: 10.1016/j.tjnut.2023.09.018. Epub 2023 Sep 27.
PubMed 37774841
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of De Novo Lipogenesis in Severity of Nonalcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT03683589
- Acronym / sponsor ID
- 2012544
- Conditions
- Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Bariatric Surgery Candidate, Obesity, Morbid
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Collaborators
- American Society for Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 21 Aug 2019 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 25 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study includes both obese men and women who are undergoing bariatric surgery
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
De novo lipogenesis
Time frame: Dec 2019
DNL will be measured directly in the liver biopsies
3 secondary outcomes
Histological scores (NAFLD activity score)
Time frame: Dec 2019
Liver enzymes
Time frame: Dec 2019
FibroScan
Time frame: Dec 2019
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
- Background: PubMed 24316260Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014 Mar;146(3):726-35. doi: 10.1053/j.gastro.2013.11.049. Epub 2013 Dec 4.
- Background: PubMed 15864352Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005 May;115(5):1343-51. doi: 10.1172/JCI23621.
- Derived from this study: PubMed 37774841Syed-Abdul MM, Moore MP, Wheeler AA, Ganga RR, Diaz-Arias A, Petroski GF, Rector RS, Ibdah JA, Parks EJ. Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease. J Nutr. 2023 Dec;153(12):3418-3429. doi: 10.1016/j.tjnut.2023.09.018. Epub 2023 Sep 27.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth J Parks, PhD principal investigator
University of Missouri-Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by University of Missouri-Columbia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
De novo lipogenesis (time frame: Dec 2019). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03683589, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2024.