Liver, Diet and Genetic Background

Liver Fat Clinical Trial

— LIDIGE  

Official title:

The Effect of Dietary Fat Quality Modification for Liver Fat Content in Participants With Different Variants in PNPLA3 Gene - Liver, Diet and Genetic Background (LIDIGE STUDY)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04644887
• Other study ID #: LIDIGE
• Status: Completed
• Phase: N/A
• Start date: January 12, 2021
• Est. completion date: December 31, 2021

Study information

• Verified date: May 2024
• Source: University of Eastern Finland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PNPLA3 rs738409 (I148M) variant is associated with hepatic liver accumulation and chronic liver diseases including non-alcoholic fatty liver disease. It has been shown that obesity augments genetic risk but studies investigating the interaction of PNPLA3 rs738409 risk variant and diet are scarce. The aim is to investigate the effect of dietary fat quality modification in participants with different variants of the PNPLA3 gene (rs738409). The primary outcome is the change in liver fat measured by magnetic resonance imaging in the randomized controlled 12-week dietary intervention trial.

Description:

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The composition of the diet, especially quality of dietary fat, contributes to the susceptibility to hepatic lipid accumulation. Saturated fatty acids (SFA), but not polyunsaturated fatty acids (PUFA) increases intrahepatic triglycerides with and without concomitant weight gain. Therefore, the modification of dietary fat quality is the key dietary approach for the prevention of NAFLD.

PNPLA3 rs738409 (I148M) variant is associated with hepatic liver accumulation and chronic liver diseases including NAFLD. It has been shown that obesity augments genetic risk but studies investigating the interaction of PNPLA3 rs738409 risk variant and diet are scarce. Therefore, the aim is to investigate the effect of dietary fat quality modification (high unsaturated fat vs. high SFA) on liver fat and lipid and glucose metabolism in participants with different variants (CC or GG) of the PNPLA3 gene.

The investigators will conduct the randomized controlled 12-week dietary intervention trial in participants with different homozygous PNPLA3 variants (CC or GG). The primary outcome of the intervention is in the amount of liver fat measured by nuclear magnetic resonance imaging (MRI). Altogether 140 homozygous participants (PNPLA3 rs738409 CC and GG) will be recruited from the Metabolic Syndrome in Men (METSIM) study. The inclusion criteria include BMI < 35 kg/m2 and age < 75 years. The main exclusion criteria include diabetes, acute illness, or current evidence of acute or chronic inflammatory or infective diseases.

Dietary guidance in the intervention group is based on the Nordic and Finnish nutrition recommendations with an emphasis on the quality of dietary fat. The aims for the intake of fatty acids will be SFA < 10 % of energy intake (E%) and mono- and polyunsaturated fatty acids (UFA) >2/3 of the total fat intake.

The diet of the control group corresponds to the average nutrient intake in the Nordic countries, i.e. the intake of SFA about 15 E% and the proportion of UFA about 50 % of total fat intake.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 60 Years to 75 Years

Eligibility

Inclusion Criteria:

• PNPLA3 rs738409, CC or GG

• Body mass index (BMI) < 35 kg/m2

• Total cholesterol < 8 mmol/l

• LDL cholesterol < 5 mmol/l

• Fasting plasma glucose < 7 mmol/l

• Plasma alanine aminotransferase (ALT) < 100 U/l

• Age 60-75 y

Exclusion Criteria:

The main exclusion criteria include acute illness or current evidence of acute or chronic inflammatory or infective diseases. No patients with hepatitis B and/or C, autoimmune hepatitis, Wilsons disease/alpha-1-antitrypsin deficiency, hemochromatosis, chronic kidney disease, unstable hypothyroidism or lipoatrophy will be accepted. No subjects with diagnosed diabetes (any type) are accepted. In addition to that, no diagnosed depression or any mental illness rendering the patients unable to understand the nature, scope and possible sequences of the study will be accepted. Alcohol abuse (daily consumption = 30 g for men and = 20 g for women) is also exclusion criteria.

Related Conditions & MeSH terms

• Liver Fat

Intervention

Other:
• Dietary intervention: Healthy diet
Dietary guidance in the intervention group is based on the Nordic and Finnish nutrition recommendations with an emphasis on the quality of dietary fat. The aims for the intake of fatty acids will be SFA < 10 % of energy intake (E%) and mono- and polyunsaturated fatty acids (UFA) >2/3 of the total fat intake. The key food products such as vegetable oil-based spread, liquid margarine and canola oil are provided to the participants. The participants are recommended to use fat free (e.g. milk, sourdough milk and yogurt) and low fat (e.g. cheese = 17%) dairy products and low-fat meat, poultry, and fish as well as natural nuts and seeds.
• Dietary intervention: Control diet
The control diet corresponds to the average nutrient intake in the Nordic countries, i.e. the intake of SFA about 15 E% and the proportion of UFA about 50 % of total fat intake. The participants of the control group will get butter-based spread for bread and cooking. They are recommended to use semi-skimmed milk (1,5 %), normal fat yogurt (~2%), normal fat cheese (~24-35 %) and avoid consumption of vegetable oils. They are allowed to eat a portion of fish and nuts once a week.

Locations

Country	Name	City	State
Finland	Institute of Public Health and Clinical Nutriton	Kuopio

Sponsors (2)

Lead Sponsor	Collaborator
University of Eastern Finland	Kuopio University Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Liver fat	The primary outcome is the change in liver fat measured by magnetic resonance imaging	12 weeks
Secondary	Hepatic condition monitored by ultrasound	The hepatic condition will be monitored by ultrasound	12 weeks
Secondary	Hepatic condition monitored by elastography	The hepatic condition will be monitored by elastography	12 weeks
Secondary	Hepatic condition monitored by calculated indexes	The hepatic condition will be monitored by calculating and comparing Fibrosis-4 index, NAFLD Fibrosis Score, hepatic steatosis index, the fatty liver index and NAFLD liver fat score.	12 weeks
Secondary	Glucose metabolism	Changes in glucose metabolism (oral glucose tolerance test, 0, 30 min and 2 h samples)	12 weeks
Secondary	Serum lipid profile	Concentrations of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides	12 weeks
Secondary	Inflammatory markers	Serum circulating concentrations of high-sensitivity C-reactive protein	12 weeks
Secondary	Plasma metabolomic profile	Mass spectrometry based metabolomics analysis	12 weeks
Secondary	Plasma lipidomic profile	Mass spectrometry based lipidomics analysis	12 weeks
Secondary	Gut microbiota	The DNA/RNA of gut microbiota will be extracted and collected for high throughput metagenomics and metatranscriptomics to observe changes in type and composition of gut microbiota.	12 weeks
Secondary	Fatty acid composition of plasma lipid fractions	Fatty acid composition of plasma phospholipids, cholesteryl esters and triglycerides	12 weeks