- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04644887
Liver, Diet and Genetic Background (LIDIGE)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Ursula Schwab, Professor
- Phone Number: +358 29 445 4528
- Email: ursula.schwab@uef.fi
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Healthy diet CC genotype
The participants will follow the intervention diet during the 12-week intervention period.
|
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.
|
ACTIVE_COMPARATOR: Control diet CC genotype
The participants will follow the control diet during the 12-week intervention period.
|
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.
|
EXPERIMENTAL: Healthy diet GG genotype
The participants will follow the intervention diet during the 12-week intervention period.
|
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.
|
ACTIVE_COMPARATOR: Control diet GG genotype
The participants will follow the control diet during the 12-week intervention period.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Liver fat
Time Frame: 12 weeks
|
The primary outcome is the change in liver fat measured by magnetic resonance imaging
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hepatic condition monitored by ultrasound
Time Frame: 12 weeks
|
The hepatic condition will be monitored by ultrasound
|
12 weeks
|
Hepatic condition monitored by elastography
Time Frame: 12 weeks
|
The hepatic condition will be monitored by elastography
|
12 weeks
|
Hepatic condition monitored by calculated indexes
Time Frame: 12 weeks
|
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
|
Glucose metabolism
Time Frame: 12 weeks
|
Changes in glucose metabolism (oral glucose tolerance test, 0, 30 min and 2 h samples)
|
12 weeks
|
Serum lipid profile
Time Frame: 12 weeks
|
Concentrations of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
|
12 weeks
|
Inflammatory markers
Time Frame: 12 weeks
|
Serum circulating concentrations of high-sensitivity C-reactive protein
|
12 weeks
|
Plasma metabolomic profile
Time Frame: 12 weeks
|
Mass spectrometry based metabolomics analysis
|
12 weeks
|
Plasma lipidomic profile
Time Frame: 12 weeks
|
Mass spectrometry based lipidomics analysis
|
12 weeks
|
Gut microbiota
Time Frame: 12 weeks
|
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
|
Fatty acid composition of plasma lipid fractions
Time Frame: 12 weeks
|
Fatty acid composition of plasma phospholipids, cholesteryl esters and triglycerides
|
12 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ursula Schwab, Professor, University of Eastern Finland
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- LIDIGE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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