Fatty Liver, NonalcoholicNCT03211299
Determinants of Liver Fat Composition
An observational study of Fatty Liver, Nonalcoholic and Insulin Sensitivity, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Excessive fat in the liver, in absence of high alcohol consumption, is diagnosed as non-alcoholic fatty liver (NAFL). NAFL prevalence is as high as 50-70% in obese people and is associated with impairments in metabolic health, e.g. insulin resistance. Read more about this study
- Who is it for?
- Ages 45 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Fatty Liver, Nonalcoholic, Insulin Sensitivity
- How many people
- 19 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Aug 2017to 17 May 2018
- Phase
- Observational
- 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 45 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Twenty-two healthy overweight/obese males and females, aged between 45-70 years and BMI between 27-35 kg/m2 will participate in the whole study. To create a continuum in liver fat content, eight subjects with liver fat content lower than 5% and 14 subjects with liver fat content higher than 5% (NAFL) will be included. At least seven volunteers with NAFL will have severely elevated hepatic fat content (liver fat percentage ≥ 15%).
Who may be able to join
- Signed informed consent
- Caucasian (people will be excluded when having a 50% or a more then 50% racial African/Asian background)
- Male or postmenopausal female
- Aged 45-70 years at start of the study
- Body mass index (BMI) 27 - 35 kg/m2
- Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
- Sedentary lifestyle (not more than 2 hours of sports per week)
Who cannot join
- Type 2 diabetes
- Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other)
- Contra-indication for MRI (which can be found in appendix I)
- Alcohol consumption of >2 servings per day
- Smoking >5 cigarettes per day
- Use of anti-coagulants
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 6229 ER
About this study
Official title: Determinants of Liver Fat Composition in Overweight and Obese Humans
Excessive fat in the liver, in absence of high alcohol consumption, is diagnosed as non-alcoholic fatty liver (NAFL). NAFL prevalence is as high as 50-70% in obese people and is associated with impairments in metabolic health, e.g. insulin resistance. Not only the amount, but also the composition of the fat stored in the liver appears to be linked to health outcome measures, such as insulin resistance, but this evidence comes mainly from animal studies. Since fat composition has been linked to health outcome measures, it is important to understand what determines the fatty acid composition of liver fat. De novo lipogenesis (DNL) and adipose tissue fat composition are factors that could determine liver fat composition. Since the end product of DNL are saturated fatty acids and as the majority of fatty acids in the liver originate from adipose tissue, both may influence hepatic fatty acid composition profoundly. Here, our primary hypothesis is that DNL is associated with the relative amount of saturated fatty acids in the liver in overweight/obese humans differing in liver fat content. Furthermore, we hypothesise that adipose tissue fat composition is associated with liver fat composition and that liver fat composition is associated with liver, muscle and whole body insulin sensitivity in overweight/obese humans differing in liver fat content. To this end, liver fat composition, adipose tissue fat composition, DNL and insulin sensitivity will be measured in overweight/obese participants differing in liver content.
Read the detailed description
Rationale: Excessive fat in the liver, in absence of high alcohol consumption, is diagnosed as nonalcoholic fatty liver (NAFL). NAFL prevalence is as high as 50-70% in obese people and is associated with impairments in metabolic health, e.g. insulin resistance. Not only the amount, but also the composition of the fat stored in the liver appears to be linked to health outcome measures, such as insulin resistance, but this evidence comes mainly from animal studies. Since fat composition has been linked to health outcome measures, it is important to understand what determines the fatty acid composition of liver fat. De novo lipogenesis (DNL) and adipose tissue fat composition are factors that could determine liver fat composition. Since the end product of DNL are saturated fatty acids and as the majority of fatty acids in the liver originate from adipose tissue, both may influence hepatic fatty acid composition profoundly. Up to now, associations between hepatic fatty acid composition, DNL and adipose tissue fatty acid composition have never been determined in the same study.
Objective: The primary objective of this study is to determine the association between DNL and hepatic %SFA in overweight/obese subjects differing in liver fat content. The secondary objectives are to determine the association between adipose tissue fat composition and liver fat composition and to determine the association between liver fat composition and whole body, liver and muscle insulin sensitivity.
Study design: This is a cross-sectional observational study. For this study a design of 3 groups with different amounts of liver fat are included, in order to create a study population with a continuum in liver fat content.
Study population: Twenty-two healthy overweight/obese males and females, aged between 45-70 years and BMI between 27-35 kg/m2 will participate in the whole study. To create a continuum in liver fat content, eight subjects with liver fat content lower than 5% and 14 subjects with liver fat content higher than 5%, of which at least seven subjects have a liver fat content of at least 15%, will be included. To be able to include enough people in each group, around 31 participants will be included in total. A part of the participants will stop participating in the study after determination of liver fat content (in case the liver fat content does not match the groups).
Main study parameters/endpoints: The primary study parameters are %SFA in the liver and DNL. %SFA in the liver will be determined using MRS and DNL will be determined by applying stable isotope techniques. The secondary study parameters are hepatic fat composition, measured as %MUFA and %PUFA in addition to %SFA using MRS, adipose tissue fat composition, determined using MRS and biopsies, and insulin sensitivity, measured by a hyperinsulinemic euglycemic 2- step clamp.
- Conditions
- Fatty Liver, Nonalcoholic, Insulin Sensitivity
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| IHL <5% | overweight and obese humans with a liver fat percentage <5% | |
| IHL 5-10% | overweight and obese humans with a liver fat percentage 5-15% | |
| IHL >15% | overweight and obese humans with a liver fat percentage >15% |
What is being measured
The primary outcome is the main question the study is designed to answer.
%SFA in the liver
expressed as relative amount of SFA to the total amount of fatty acids (determined by magnetic resonance spectroscopy)
Measured: 20 minutes
DNL
expressed as percentage of palmitate in VLDL-TG originating from DNL (determined by use of deuterium water)
Measured: 16 hours
Secondary outcomes (7)
Liver fat composition
expressed as relative amount of MUFA and PUFA to the total amount of fatty acids, in addition to %SFA (determined by magnetic resonance spectroscopy)
Measured: 20 minutes
Adipose tissue fat composition
expressed as relative amount of SFA, MUFA and PUFA to the total amount of fatty acids (determined by magnetic resonance spectroscopy and from subcutaneous adipose tissue biopsy)
Measured: 20 minutes
Adipose tissue fat composition
expressed as relative amount of linoleic acid, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the total amount of fatty acids (determined from subcutaneous adipose tissue biopsy)
Measured: 15 minutes
Hepatic insulin sensitivity
expressed as % suppression of endogenous glucose production (EGP)(determined by hyperinsulinemic euglycemic clamp).
Measured: 8.5 hours
Muscle insulin sensitivity
expressed as determinants/markers for muscle insulin sensitivity in muscle biopsy (oxphos, GLUT4, intramyocellular lipids (IMCL).
Measured: 15 minutes
peripheral insulin sensitivity
expressed as rate of disappearance (Rd) in μmol/kg/min (determined by hyperinsulinemic euglycemic clamp).
Measured: 8.5 hours
whole body insulin sensitivity
expressed as glucose infusion rate (GIR) in μmol/kg/min (determined by hyperinsulinemic euglycemic clamp).
Measured: 8.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2017
- Study start15 Aug 2017
- Primary completion5 May 2018
- Study completion17 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fatty Liver, NonalcoholicStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Unilever R&D
- Responsible party
- Sponsor
- Investigators
- Vera B Schrauwen, Dr, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211299
- Sponsor's protocol ID
- NL60263.068.16
- Status last verified
- Jun 2018
- First submitted
- 3 Jul 2017
- Last updated
- 4 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Roumans KHM, Lindeboom L, Veeraiah P, Remie CME, Phielix E, Havekes B, Bruls YMH, Brouwers MCGJ, Stahlman M, Alssema M, Peters HPF, de Mutsert R, Staels B, Taskinen MR, Boren J, Schrauwen P, Schrauwen-Hinderling VB. Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance. Nat Commun. 2020 Apr 20;11(1):1891. doi: 10.1038/s41467-020-15684-0.
PubMed 32312974
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determinants of Liver Fat Composition in Overweight and Obese Humans
- ClinicalTrials.gov ID
- NCT03211299
- Acronym / sponsor ID
- NL60263.068.16
- Conditions
- Fatty Liver, Nonalcoholic, Insulin Sensitivity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Unilever R&D
- Study start
- 15 Aug 2017 (actual)
- Primary completion
- 5 May 2018 (actual)
- Study completion
- 17 May 2018 (actual)
- First posted
- 7 Jul 2017 (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.
Excessive fat in the liver, in absence of high alcohol consumption, is diagnosed as non-alcoholic fatty liver (NAFL). NAFL prevalence is as high as 50-70% in obese people and is associated with impairments in metabolic health, e.g. insulin resistance. Not only the amount, but also the composition of the fat stored in the liver appears to be linked to health outcome measures, such as insulin resistance, but this evidence comes mainly from animal studies. Since fat composition has been linked to health outcome measures, it is important to understand what determines the fatty acid composition of liver fat. De novo lipogenesis (DNL) and adipose tissue fat composition are factors that could determine liver fat composition. Since the end product of DNL are saturated fatty acids and as the majority of fatty acids in the liver originate from adipose tissue, both may influence hepatic fatty acid composition profoundly. Here, our primary hypothesis is that DNL is associated with the relative amount of saturated fatty acids in the liver in overweight/obese humans differing in liver fat content. Furthermore, we hypothesise that adipose tissue fat composition is associated with liver fat composition and that liver fat composition is associated with liver, muscle and whole body insulin sensitivity in overweight/obese humans differing in liver fat content. To this end, liver fat composition, adipose tissue fat composition, DNL and insulin sensitivity will be measured in overweight/obese participants differing in liver content.
Detailed description
Rationale: Excessive fat in the liver, in absence of high alcohol consumption, is diagnosed as nonalcoholic fatty liver (NAFL). NAFL prevalence is as high as 50-70% in obese people and is associated with impairments in metabolic health, e.g. insulin resistance. Not only the amount, but also the composition of the fat stored in the liver appears to be linked to health outcome measures, such as insulin resistance, but this evidence comes mainly from animal studies. Since fat composition has been linked to health outcome measures, it is important to understand what determines the fatty acid composition of liver fat. De novo lipogenesis (DNL) and adipose tissue fat composition are factors that could determine liver fat composition. Since the end product of DNL are saturated fatty acids and as the majority of fatty acids in the liver originate from adipose tissue, both may influence hepatic fatty acid composition profoundly. Up to now, associations between hepatic fatty acid composition, DNL and adipose tissue fatty acid composition have never been determined in the same study.
Objective: The primary objective of this study is to determine the association between DNL and hepatic %SFA in overweight/obese subjects differing in liver fat content. The secondary objectives are to determine the association between adipose tissue fat composition and liver fat composition and to determine the association between liver fat composition and whole body, liver and muscle insulin sensitivity.
Study design: This is a cross-sectional observational study. For this study a design of 3 groups with different amounts of liver fat are included, in order to create a study population with a continuum in liver fat content.
Study population: Twenty-two healthy overweight/obese males and females, aged between 45-70 years and BMI between 27-35 kg/m2 will participate in the whole study. To create a continuum in liver fat content, eight subjects with liver fat content lower than 5% and 14 subjects with liver fat content higher than 5%, of which at least seven subjects have a liver fat content of at least 15%, will be included. To be able to include enough people in each group, around 31 participants will be included in total. A part of the participants will stop participating in the study after determination of liver fat content (in case the liver fat content does not match the groups).
Main study parameters/endpoints: The primary study parameters are %SFA in the liver and DNL. %SFA in the liver will be determined using MRS and DNL will be determined by applying stable isotope techniques. The secondary study parameters are hepatic fat composition, measured as %MUFA and %PUFA in addition to %SFA using MRS, adipose tissue fat composition, determined using MRS and biopsies, and insulin sensitivity, measured by a hyperinsulinemic euglycemic 2- step clamp.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IHL <5% | – | –overweight and obese humans with a liver fat percentage <5% |
| IHL 5-10% | – | –overweight and obese humans with a liver fat percentage 5-15% |
| IHL >15% | – | –overweight and obese humans with a liver fat percentage >15% |
Who may qualify
- Ages
- 45 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Twenty-two healthy overweight/obese males and females, aged between 45-70 years and BMI between 27-35 kg/m2 will participate in the whole study. To create a continuum in liver fat content, eight subjects with liver fat content lower than 5% and 14 subjects with liver fat content higher than 5% (NAFL) will be included. At least seven volunteers with NAFL will have severely elevated hepatic fat content (liver fat percentage ≥ 15%).
Key inclusion criteria (7 listed)
- Signed informed consent
- Caucasian (people will be excluded when having a 50% or a more then 50% racial African/Asian background)
- Male or postmenopausal female
- Aged 45-70 years at start of the study
- Body mass index (BMI) 27 - 35 kg/m2
Key exclusion criteria (6 listed)
- Type 2 diabetes
- Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other)
- Contra-indication for MRI (which can be found in appendix I)
- Alcohol consumption of >2 servings per day
- Smoking >5 cigarettes per day
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
%SFA in the liver
Time frame: 20 minutes
expressed as relative amount of SFA to the total amount of fatty acids (determined by magnetic resonance spectroscopy)
DNL
Time frame: 16 hours
expressed as percentage of palmitate in VLDL-TG originating from DNL (determined by use of deuterium water)
7 secondary outcomes
Liver fat composition
Time frame: 20 minutes
Adipose tissue fat composition
Time frame: 20 minutes
Adipose tissue fat composition
Time frame: 15 minutes
Hepatic insulin sensitivity
Time frame: 8.5 hours
Muscle insulin sensitivity
Time frame: 15 minutes
peripheral insulin sensitivity
Time frame: 8.5 hours
whole body insulin sensitivity
Time frame: 8.5 hours
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 4 Jun 2018.
- Derived from this study: PubMed 32312974Roumans KHM, Lindeboom L, Veeraiah P, Remie CME, Phielix E, Havekes B, Bruls YMH, Brouwers MCGJ, Stahlman M, Alssema M, Peters HPF, de Mutsert R, Staels B, Taskinen MR, Boren J, Schrauwen P, Schrauwen-Hinderling VB. Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance. Nat Commun. 2020 Apr 20;11(1):1891. doi: 10.1038/s41467-020-15684-0.
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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.
Vera B Schrauwen, Dr principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fatty Liver, Nonalcoholic and Insulin Sensitivity, run by Maastricht University Medical Center at 1 site in Netherlands.
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 6 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 4 Jun 2018. 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 Netherlands. 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?
%SFA in the liver (time frame: 20 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03211299, which also lists 1 linked publication.
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 4 Jun 2018; AzTrials last refreshed its copy on 4 Nov 2026.