Clinical trial NCT04644887: Liver, Diet and Genetic Background
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Fat
Keywords: human
diet
dietary fat
liver fat
genotype
nutrigenomics
Lead sponsor: University of Eastern Finland
Sponsor class: OTHER
Collaborators: name: Kuopio University Hospital
First posted: 2020-11-25
Enrollment: 99
Sex: MALE
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Liver fat
timeFrame: 12 weeks
Secondary outcomes:
measure: Hepatic condition monitored by ultrasound
timeFrame: 12 weeks
measure: Hepatic condition monitored by elastography
timeFrame: 12 weeks
measure: Hepatic condition monitored by calculated indexes
timeFrame: 12 weeks
measure: Glucose metabolism
timeFrame: 12 weeks
measure: Serum lipid profile
timeFrame: 12 weeks
measure: Inflammatory markers
timeFrame: 12 weeks
measure: Plasma metabolomic profile
timeFrame: 12 weeks
measure: Plasma lipidomic profile
timeFrame: 12 weeks
measure: Gut microbiota
timeFrame: 12 weeks
measure: Fatty acid composition of plasma lipid fractions
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: Institute of Public Health and Clinical Nutriton
Study officials:
affiliation: University of Eastern Finland
name: Ursula Schwab, Professor
role: PRINCIPAL_INVESTIGATOR
References: