Liver FatLIDIGENCT04644887
Liver, Diet and Genetic Background
A study testing Dietary intervention: Healthy diet in people with Liver Fat, run by University of Eastern Finland at 1 site in Finland.
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. Read more about this study
- Who is it for?
- Ages 60 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Liver Fat
- What is being tested?
- Dietary intervention: Healthy diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteFinland
- Study dates
- 12 Jan 2021to 31 Dec 2021
- 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 60 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Liver Fat
- Being tested
- Dietary intervention: Healthy diet, Dietary intervention: Control diet
- Keywords
- human, diet, dietary fat, liver fat, genotype, nutrigenomics
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary intervention: Healthy dietOther
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 dietOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy diet CC genotype | Experimental | The participants will follow the intervention diet during the 12-week intervention period. Receives: Other: Dietary intervention: Healthy diet |
| Control diet CC genotype | Active comparator | The participants will follow the control diet during the 12-week intervention period. Receives: Other: Dietary intervention: Control diet |
| Healthy diet GG genotype | Experimental | The participants will follow the intervention diet during the 12-week intervention period. Receives: Other: Dietary intervention: Healthy diet |
| Control diet GG genotype | Active comparator | The participants will follow the control diet during the 12-week intervention period. Receives: Other: Dietary intervention: Control diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver fat
The primary outcome is the change in liver fat measured by magnetic resonance imaging
Measured: 12 weeks
Secondary outcomes (10)
Hepatic condition monitored by ultrasound
The hepatic condition will be monitored by ultrasound
Measured: 12 weeks
Hepatic condition monitored by elastography
The hepatic condition will be monitored by elastography
Measured: 12 weeks
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.
Measured: 12 weeks
Glucose metabolism
Changes in glucose metabolism (oral glucose tolerance test, 0, 30 min and 2 h samples)
Measured: 12 weeks
Serum lipid profile
Concentrations of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides
Measured: 12 weeks
Inflammatory markers
Serum circulating concentrations of high-sensitivity C-reactive protein
Measured: 12 weeks
Plasma metabolomic profile
Mass spectrometry based metabolomics analysis
Measured: 12 weeks
Plasma lipidomic profile
Mass spectrometry based lipidomics analysis
Measured: 12 weeks
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.
Measured: 12 weeks
Fatty acid composition of plasma lipid fractions
Fatty acid composition of plasma phospholipids, cholesteryl esters and triglycerides
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start12 Jan 2021
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver FatStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Eastern Finland
- Sponsor type
- University, hospital or other
- Collaborators
- Kuopio University Hospital
- Responsible party
- Sponsor
- Investigators
- Ursula Schwab, Professor, Principal investigator, University of Eastern Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04644887
- Sponsor's protocol ID
- LIDIGE
- Acronym
- LIDIGE
- Status last verified
- May 2024
- First submitted
- 18 Nov 2020
- Last updated
- 9 May 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 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04644887
- Acronym / sponsor ID
- LIDIGE / LIDIGE
- Conditions
- Liver Fat
- Keywords
- human, diet, dietary fat, liver fat, genotype, nutrigenomics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- University of Eastern FinlandUniversity, hospital or other
- Collaborators
- Kuopio University Hospital
- Study start
- 12 Jan 2021 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 25 Nov 2020 (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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy diet CC genotype | Experimental | Other: Dietary intervention: Healthy dietThe participants will follow the intervention diet during the 12-week intervention period. |
| Control diet CC genotype | Active comparator | Other: Dietary intervention: Control dietThe participants will follow the control diet during the 12-week intervention period. |
| Healthy diet GG genotype | Experimental | Other: Dietary intervention: Healthy dietThe participants will follow the intervention diet during the 12-week intervention period. |
| Control diet GG genotype | Active comparator | Other: Dietary intervention: Control dietThe participants will follow the control diet during the 12-week intervention period. |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (1 listed)
- 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.
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 |
|---|---|---|
| Dietary intervention: Healthy dietDietary 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. | Other | Healthy diet CC genotype, Healthy diet GG genotype |
| Dietary intervention: Control dietThe 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. | Other | Control diet CC genotype, Control diet GG genotype |
Primary outcome
Liver fat
Time frame: 12 weeks
The primary outcome is the change in liver fat measured by magnetic resonance imaging
10 secondary outcomes
Hepatic condition monitored by ultrasound
Time frame: 12 weeks
Hepatic condition monitored by elastography
Time frame: 12 weeks
Hepatic condition monitored by calculated indexes
Time frame: 12 weeks
Glucose metabolism
Time frame: 12 weeks
Serum lipid profile
Time frame: 12 weeks
Inflammatory markers
Time frame: 12 weeks
Plasma metabolomic profile
Time frame: 12 weeks
Plasma lipidomic profile
Time frame: 12 weeks
Gut microbiota
Time frame: 12 weeks
Fatty acid composition of plasma lipid fractions
Time frame: 12 weeks
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 9 May 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.
Ursula Schwab, Professor principal investigator
University of Eastern Finland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary intervention: Healthy diet in people with Liver Fat, run by University of Eastern Finland at 1 site in Finland.
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 7 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 9 May 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 Finland. 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?
Liver fat (time frame: 12 weeks). 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 9 May 2024.