Nonalcoholic Fatty Liver Disease (NAFLD)LITONASNCT03836443
Postprandial Lipotoxicity and Nonalcoholic Fatty Liver Disease
A study testing western diet" meal in people with Nonalcoholic Fatty Liver Disease (NAFLD), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Nonalcoholic fatty liver disease (NAFLD) is mainly considered a nutrition-related disease and life-style/diet interventions showed some promising results. But in spite of this, there are no available markers to efficiently guide interventions. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Nonalcoholic Fatty Liver Disease (NAFLD)
- What is being tested?
- western diet" meal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 14 Feb 2019to 22 Jun 2023
- Phase
- Interventional
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histological proven NAFLD (liver biopsy <6 months); hospitalised or outpatients followed up for NAFLD; patients giving their consent for the study; patients covered by health insurance.
Who cannot join
- history of excessive alcohol consumption (>20 g/day for males and >10 g/day for females) or other cause of liver injury (viral hepatitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, drug-induced hepatitis, or others); cirrhosis; ongoing hypolipemiant treatment; diabetes; Chronic diarrhea; severe associated disease;Taking antibiotics or probiotics in the last 3 months; Chronic inflammatory bowel disease; Weight ≤70Kg and hemoglobin level ≤7g/dl; Allergy to or refusal of any of the elements of the meal provided.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lipid Metabolism, Lipotoxicity and Nonalcoholic Fatty Liver Disease: Implication of Postprandial Cytotoxic Lipids
Nonalcoholic fatty liver disease (NAFLD) is mainly considered a nutrition-related disease and life-style/diet interventions showed some promising results. But in spite of this, there are no available markers to efficiently guide interventions. the hypothesize put farth by the investigators is that NAFLD patients develop postprandial abnormalities of plasma lipids upon "western diet" challenge, more severe in steatohepatitis (NASH) than in pure steatosis (NAFL), promoting liver injury. Our study aims to evaluate the presence of toxic lipids (such as free-fatty acids, ceramides, diacylglycerols, sphingolipids) in postprandial state after ingestion of a "western diet" in NAFLD patients. Consecutive patients (group 1: NAFL patients; group 2: NASH patients) with biopsy-proven NAFLD (liver biopsy < 6 months) will be recruited during a period of 12 month. Blood samples will be drawn at fasting, 2hours, 4hours, 6hours and 8hours after ingestion of a "western diet" meal. Plasma lipid profiles using lipidomics, circulating markers of liver injury and inflammation will be analyzed. the investigators will also assess the hepatotoxicity of plasma from NAFL or NASH patients in-vitro.
Read the detailed description
Factors driving progression from steatosis (NAFL) to steatohepatitis (NASH) in patients with non-alcoholic fatty liver disease (NAFLD) remain largely unknown. Considerable data now indicate that steatosis per se is not a hepatotoxic event and may represent in fact a protective mechanism against free fatty acid (FFA)-induced toxicity. the investigators previously showed that Kupffer cells from NASH mice accumulate more toxic lipids (ceramides, diacylglycerols, sphingolipids) enhancing their proinflammatory polarization. Therefore, "quality" of accumulating lipids rather than "quantity" may play a central role in NAFLD progression. This is a pilot comparative study aiming to evaluate the presence of toxic lipids (such as free-fatty acids, ceramides, diacylglycerols, sphingolipids) in postprandial state after ingestion of a "western diet" in NAFL and NASH patients. The secondary outcomes were: to evaluate the relationship between postprandial circulating lipids and markers of liver injury and proinflammatory cytokines; to evaluate hepatotoxicity of postprandial lipids in vitro. A total of 24 consecutive patients (group 1: 12 NAFL patients; group 2: 12 NASH patients) with biopsy-proven NAFLD (liver biopsy < 6 months) will be recruited. A dietary evaluation covering the 2 previous weeks will be performed. Detailed anthropometric data will be collected (body mass index, waist and hip circumferences, abdominal height, cutaneous skinfolds) and serum metabolic parameters (standard lipid profile, lipoprotein levels, fasting plasma glucose, insulin levels, C-peptide levels, hemoglobin A1c) will be evaluated. After a 12hours overnight fast, patients will undergo an oral "western diet" test consisting in the ingestion of a high saturated fat, high refined sugar, high fructose-meal called "western diet" (800 kcal/meal). Blood samples will be drawn at fasting and then 2, 4, 6 and 8hours after ingestion of the standard meal. Each time plasma and serum samples will be stored at -80°C for subsequent analysis. Lipidomics will be used to quantify each plasma lipid class (neutral lipids, phospholipids and fatty acid methyl esters). Serum levels of cytokines will be assessed using multiple assay technology. Markers of liver injury will be assessed (aminotransferases, Keratin 18 fragments, microRNA-122) in the serum. Hepatocytes will be cultured with plasma from NAFL or NASH patients, and incubated overnight. In vitro hepatotoxicity will be evaluated using TUNEL assay, MTT assay and LDH release assay. the investigators anticipate that inflammation together with hepatocyte death will occur in NAFLD patients who develop specific postprandial plasma lipid changes with an increase in toxic lipid levels. Such patients may develop more severe liver lesions (inflammation, fibrosis/cirrhosis) and benefit of interventions. Identification of a toxic plasma lipid profile may help choosing the adequate diet in order to prevent deleterious lipid formation. Identification of a toxic postprandial plasma lipid signature specific to hepatotoxicity may also serve to develop a discrimination index to be further validated in clinical practice.
- Conditions
- Nonalcoholic Fatty Liver Disease (NAFLD)
- Being tested
- western diet" meal
- Keywords
- NAFLD, toxic lipids, postprandial lipotoxicity
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
western diet" mealOther
A "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal) after an overnight fast.
| Study group | Role | What they receive |
|---|---|---|
| NAFL patients (group 1) | Active comparator | A "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal). Receives: Other: western diet" meal |
| NASH patients (group 2) | Active comparator | A "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal). Receives: Other: western diet" meal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postprandial changes of plasma lipid fractions measured by lipidomic analysis and expressed as nmolof lipid/ml
Lipidomic analysis of plasma lipid fractions expressed in ηm/ml after 12 hours of fasting and in the postprandial period (2h, 4h, 6h, 8h).
Measured: Plasma samples will be collected at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal to assess postprandial lipid fraction changes
Secondary outcomes (4)
Circulating markers of liver injury (AST, ALT, cytokeratin 18 fragments, microRNA-122) and serum cytokines (TNF-α, IL-6, IL-1β, IL-8).
Circulating markers of liver injury (AST, ALT, cytokeratin 18 fragments, microRNA-122) and serum cytokines (TNF-α, IL-6, IL-1β, IL-8) will be measured after 12 hours of fasting and in the postprandial period (2h, 4h, 6h, 8h) in patients with NAFLD
Measured: After a 12hours overnight fast and then at 2, 4, 6 and 8hours after ingestion of the "western diet" meal.
Cytotoxic effect of postprandial plasma on hepatocytes in-vitro
Hepatocytes will be cultured with postprandial plasma from NAFL or NASH patients, and incubated overnight. In-vitro hepatotoxicity will be evaluated using TUNEL assay, MTT assay and LDH release assay.
Measured: Plasma samples at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal.
The effect of supernatants from hepatocyte cultures exposed to patient plasma on human macrophages in vitro
Human macrophage will be cultured in vitro with supernatants from hepatocyte cultures exposed to patient plasma
Measured: Plasma samples at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal.
Bacterial microbiome profiles
Bacterial microbiome profiles will be measured by the pyrosequencing technique of 16S RNA
Measured: The day before or the morning before ingestion of the "western diet" meal.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2019
- Study start14 Feb 2019
- Primary completion22 Jun 2023
- Study completion22 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonalcoholic Fatty Liver Disease (NAFLD)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal) after an overnight fast.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cosmin VOICAN, Principal investigator, AP-HP, Beclere Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03836443
- Sponsor's protocol ID
- D20180507
- Acronym
- LITONAS
- Status last verified
- Apr 2023
- First submitted
- 17 Jan 2019
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lipid Metabolism, Lipotoxicity and Nonalcoholic Fatty Liver Disease: Implication of Postprandial Cytotoxic Lipids
- ClinicalTrials.gov ID
- NCT03836443
- Acronym / sponsor ID
- LITONAS / D20180507
- Conditions
- Nonalcoholic Fatty Liver Disease (NAFLD)
- Keywords
- NAFLD, toxic lipids, postprandial lipotoxicity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 14 Feb 2019 (actual)
- Primary completion
- 22 Jun 2023 (actual)
- Study completion
- 22 Jun 2023 (actual)
- First posted
- 11 Feb 2019 (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.
Nonalcoholic fatty liver disease (NAFLD) is mainly considered a nutrition-related disease and life-style/diet interventions showed some promising results. But in spite of this, there are no available markers to efficiently guide interventions. the hypothesize put farth by the investigators is that NAFLD patients develop postprandial abnormalities of plasma lipids upon "western diet" challenge, more severe in steatohepatitis (NASH) than in pure steatosis (NAFL), promoting liver injury. Our study aims to evaluate the presence of toxic lipids (such as free-fatty acids, ceramides, diacylglycerols, sphingolipids) in postprandial state after ingestion of a "western diet" in NAFLD patients. Consecutive patients (group 1: NAFL patients; group 2: NASH patients) with biopsy-proven NAFLD (liver biopsy < 6 months) will be recruited during a period of 12 month. Blood samples will be drawn at fasting, 2hours, 4hours, 6hours and 8hours after ingestion of a "western diet" meal. Plasma lipid profiles using lipidomics, circulating markers of liver injury and inflammation will be analyzed. the investigators will also assess the hepatotoxicity of plasma from NAFL or NASH patients in-vitro.
Detailed description
Factors driving progression from steatosis (NAFL) to steatohepatitis (NASH) in patients with non-alcoholic fatty liver disease (NAFLD) remain largely unknown. Considerable data now indicate that steatosis per se is not a hepatotoxic event and may represent in fact a protective mechanism against free fatty acid (FFA)-induced toxicity. the investigators previously showed that Kupffer cells from NASH mice accumulate more toxic lipids (ceramides, diacylglycerols, sphingolipids) enhancing their proinflammatory polarization. Therefore, "quality" of accumulating lipids rather than "quantity" may play a central role in NAFLD progression. This is a pilot comparative study aiming to evaluate the presence of toxic lipids (such as free-fatty acids, ceramides, diacylglycerols, sphingolipids) in postprandial state after ingestion of a "western diet" in NAFL and NASH patients. The secondary outcomes were: to evaluate the relationship between postprandial circulating lipids and markers of liver injury and proinflammatory cytokines; to evaluate hepatotoxicity of postprandial lipids in vitro. A total of 24 consecutive patients (group 1: 12 NAFL patients; group 2: 12 NASH patients) with biopsy-proven NAFLD (liver biopsy < 6 months) will be recruited. A dietary evaluation covering the 2 previous weeks will be performed. Detailed anthropometric data will be collected (body mass index, waist and hip circumferences, abdominal height, cutaneous skinfolds) and serum metabolic parameters (standard lipid profile, lipoprotein levels, fasting plasma glucose, insulin levels, C-peptide levels, hemoglobin A1c) will be evaluated. After a 12hours overnight fast, patients will undergo an oral "western diet" test consisting in the ingestion of a high saturated fat, high refined sugar, high fructose-meal called "western diet" (800 kcal/meal). Blood samples will be drawn at fasting and then 2, 4, 6 and 8hours after ingestion of the standard meal. Each time plasma and serum samples will be stored at -80°C for subsequent analysis. Lipidomics will be used to quantify each plasma lipid class (neutral lipids, phospholipids and fatty acid methyl esters). Serum levels of cytokines will be assessed using multiple assay technology. Markers of liver injury will be assessed (aminotransferases, Keratin 18 fragments, microRNA-122) in the serum. Hepatocytes will be cultured with plasma from NAFL or NASH patients, and incubated overnight. In vitro hepatotoxicity will be evaluated using TUNEL assay, MTT assay and LDH release assay. the investigators anticipate that inflammation together with hepatocyte death will occur in NAFLD patients who develop specific postprandial plasma lipid changes with an increase in toxic lipid levels. Such patients may develop more severe liver lesions (inflammation, fibrosis/cirrhosis) and benefit of interventions. Identification of a toxic plasma lipid profile may help choosing the adequate diet in order to prevent deleterious lipid formation. Identification of a toxic postprandial plasma lipid signature specific to hepatotoxicity may also serve to develop a discrimination index to be further validated in clinical practice.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal) after an overnight fast.
| Arm | Type | Receives |
|---|---|---|
| NAFL patients (group 1) | Active comparator | Other: western diet" mealA "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal). |
| NASH patients (group 2) | Active comparator | Other: western diet" mealA "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- histological proven NAFLD (liver biopsy <6 months); hospitalised or outpatients followed up for NAFLD; patients giving their consent for the study; patients covered by health insurance.
Key exclusion criteria (1 listed)
- history of excessive alcohol consumption (>20 g/day for males and >10 g/day for females) or other cause of liver injury (viral hepatitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, drug-induced hepatitis, or others); cirrhosis; ongoing hypolipemiant treatment; diabetes; Chronic diarrhea; severe associated disease;Taking antibiotics or probiotics in the last 3 months; Chronic inflammatory bowel disease; Weight ≤70Kg and hemoglobin level ≤7g/dl; Allergy to or refusal of any of the elements of the meal provided.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| western diet" mealA "western diet" meal (high saturated fat, high refined sugar, high fructose) will be administered in each group (800 kcal/meal) after an overnight fast. | Other | NAFL patients (group 1), NASH patients (group 2) |
Primary outcome
Postprandial changes of plasma lipid fractions measured by lipidomic analysis and expressed as nmolof lipid/ml
Time frame: Plasma samples will be collected at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal to assess postprandial lipid fraction changes
Lipidomic analysis of plasma lipid fractions expressed in ηm/ml after 12 hours of fasting and in the postprandial period (2h, 4h, 6h, 8h).
4 secondary outcomes
Circulating markers of liver injury (AST, ALT, cytokeratin 18 fragments, microRNA-122) and serum cytokines (TNF-α, IL-6, IL-1β, IL-8).
Time frame: After a 12hours overnight fast and then at 2, 4, 6 and 8hours after ingestion of the "western diet" meal.
Cytotoxic effect of postprandial plasma on hepatocytes in-vitro
Time frame: Plasma samples at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal.
The effect of supernatants from hepatocyte cultures exposed to patient plasma on human macrophages in vitro
Time frame: Plasma samples at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal.
Bacterial microbiome profiles
Time frame: The day before or the morning before ingestion of the "western diet" meal.
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 13 Mar 2024.
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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.
Cosmin VOICAN principal investigator
AP-HP, Beclere Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing western diet" meal in people with Nonalcoholic Fatty Liver Disease (NAFLD), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 1 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 13 Mar 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 France. 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?
Postprandial changes of plasma lipid fractions measured by lipidomic analysis and expressed as nmolof lipid/ml (time frame: Plasma samples will be collected at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal to assess postprandial lipid fraction changes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2024; AzTrials last refreshed its copy on 7 Nov 2026.