Postprandial Lipotoxicity and Nonalcoholic Fatty Liver Disease

NCT03836443 | Completed

• 1 other identifier: D20180507
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Nonalcoholic Fatty Liver Disease (NAFLD)

Keywords

NAFLD, toxic lipids, postprandial lipotoxicity

Outcome Measures

Primary Outcomes (1)

• 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).

  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).

  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

  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

  Plasma samples at 2hours, 4hours, 6hours and 8hours after ingestion of the "western diet" meal.

• Bacterial microbiome profiles

  The day before or the morning before ingestion of the "western diet" meal.

Study Arms (2)

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).

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).

Other: western diet" meal

Interventions

western diet" meal OTHER

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.

NAFL patients (group 1); NASH patients (group 2)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Kremlin Bicetre hospital

Le Kremlin-Bicêtre, France

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Cosmin VOICAN

  AP-HP, Beclere Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: January 17, 2019
• First Posted: February 11, 2019
• Study Start: February 14, 2019
• Primary Completion: June 22, 2023
• Study Completion: June 22, 2023
• Last Updated: March 13, 2024

Record last verified: 2023-04

Locations

FR (1)