Non-alcoholic Fatty Liver DiseaseLINCNCT00714129
De Novo Lipogenesis, Lipid and Carbohydrate Metabolism in Non-alcoholic Fatty Liver Disease
A study testing Dietary intervention (calorie restricted diet) in people with Non-alcoholic Fatty Liver Disease and Diabetes, run by University of California, San Francisco at 1 site in United States.
Trial summary
The worldwide epidemic of obesity is paralleled with increased cases of non-alcoholic liver disease (liver fat accumulation) and diabetes. Fat belongs in the adipose tissue, and if excess fat accumulates in the liver or muscle, these tissues cannot use sugar efficiently. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease, Diabetes
- What is being tested?
- Dietary intervention (calorie restricted diet)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to 12 Oct 2012
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- In the steatotic subjects, steatosis will be diagnosed by MRS or liver biopsy in which >33% of the hepatocytes will contain fat. Non-steatotic controls will not have biopsies since they are not medically warranted; thus, to ensure they do not have steatosis they will undergo MRS during screening and have a total lipid: unsuppressed water < 0.05.
Who cannot join
- Habitual consumption of alcohol > 20 g/day for men and 10 g/day for women
- Confirmed HIV-1 infection, Hgb <13 g/dL for males and <12 g/dL for females
- Abnormal hepatitis B or C serology
- Diabetes or current use of any antidiabetic or hypolipidemic agents
- Presence of metal-containing substances in the body (e.g. a fragment in the eye, aneurysm clips, ear implants, spinal nerve stimulators or a pacemaker)
- Weight over 350 pounds or severe claustrophobia, which would preclude the MR studies
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- Any condition that would preclude adherence to the protocol or the ability to provide informed consent
- Change in body weight >5% within the preceding 6 months (by self-report)
- Known intolerance, allergy or hypersensitivity to fructose
- Pregnancy or lactation (for women); OR
- Any other condition that, in the opinion of the investigators, would put the subject at risk.
Trial locations and contacts
1 site in 1 country.
About this study
The worldwide epidemic of obesity is paralleled with increased cases of non-alcoholic liver disease (liver fat accumulation) and diabetes. Fat belongs in the adipose tissue, and if excess fat accumulates in the liver or muscle, these tissues cannot use sugar efficiently. It has been discovered that when large quantities of fructose (a sugar present in soft drinks) are consumed, the conversion of carbohydrate (CHO) to fat in the liver increases.
We hypothesize that: 1) subjects with fatty liver have a higher CHO uptake and conversion to fat in their liver when compared to matched control subjects with normal liver fat content; and that: 2) when subjects with fatty liver are fed a diet limiting fructose and simple sugars will decrease their liver CHO fat content. This reduction in liver fat will normalize the way the liver responds to sugar and insulin, reversing the pre-diabetic state.
Read more
The measurement of these parameters will be done using state-of-the-art techniques such as safe non-radioactive isotope tracers and non-invasive magnetic resonance spectroscopy.
For more information, please call 415-206-5532 for a phone screening
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD) is the most common liver ailment in developed countries. Fatty liver - steatosis - affects up to one third of the population. Its prevalence is rising and seems to parallel the global increase in obesity and type-2 diabetes. The etiology of NAFLD in humans is not well understood. We propose that the hepatic conversion of carbohydrates (CHO) to lipids (de novo lipogenesis, DNL) is a key factor in the accumulation of excess liver fat and the accompanying dyslipidemia and hepatic insulin resistance; and that suppressing DNL by diet will reduce liver fat and improve both lipid and carbohydrate metabolism in patients with steatosis. These hypotheses are based on studies in which we and others have established that fractional hepatic DNL can vary dramatically depending on the diet and/or health status of a subject; and, in particular, that dietary fructose is a potent lipogenic stimulus. In this proposal we will perform CRC-based studies to compare the rates of DNL and very low density lipoprotein (VLDL) kinetics in steatotic and matched non-steatotic controls and evaluate their relationship to lipid profiles and hepatic and whole-body insulin resistance and overall carbohydrate metabolism (Aim1). The steatotic individuals whose habitual intake of fructose and other simple sugars exceeds 15% of total energy intake will then be randomized to consume one of two low-fat diets that differ only in CHO type to determine whether diet-induced changes in DNL affect liver fat flux and content and hepatic, whole-body insulin sensitivity, and overall carbohydrate metabolism (Aim 2). We hypothesize that a diet that is rich in complex CHO will achieve greater decreases in DNL and liver fat than one that contains typical amounts of simple CHO, including fructose. This dietary intervention study includes a 6-week 25% energy restriction outpatient phase to promote moderate weight loss and improve insulin sensitivity, followed by a two weeks weight maintenance with the last 4 days as an inpatient stay during which all of the studies performed at baseline (Aim 1) will be repeated. State-of-the-art stable isotope techniques will be used to assess hepatic DNL, apoB100 turnover, VLDL-triglyceride (TG) fluxes, and lipolysis under fasting and fed conditions. Hepatic and extra-hepatic insulin sensitivity will be measured using hyperinsulinemic-euglycemic clamps and stable isotope studies of endogenous glucose production and glycogen flux. Liver and muscle fat will be measured by proton magnetic resonance spectroscopy (MRS), visceral fat by magnetic resonance imaging (MRI), and whole-body composition by dual-energy X-ray absorptiometry (DEXA). These studies will allow us to evaluate the importance of DNL as a mechanism modulating liver fat content and flux, and the significance of CHO quality in dietary guidance for steatotic patients.
- Conditions
- Non-alcoholic Fatty Liver Disease, Diabetes
- Being tested
- Dietary intervention (calorie restricted diet)
- Keywords
- Steatosis, Diabetes
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary intervention (calorie restricted diet)Other
Participants in Aim 2 will receive a calorie restricted diet. This group will receive all their food for approximately 8 weeks which is the similar composition of their current diet.
Dietary intervention (calorie restricted diet)Other
Participants in Aim 2 will receive a calorie restricted diet. This group will receive all their food for approximately 8 weeks which is lower in simple sugars, specifically fructose.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Weight loss diet - normal diet Receives: Other: Dietary intervention (calorie restricted diet) |
| 2 | Experimental | Weight loss diet - low in simple sugars (specifically fructose) Receives: Other: Dietary intervention (calorie restricted diet) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stable isotopic and magnetic resonance measures to determine the changes in lipid and carbohydrate metabolism after dietary intervention
Measured: approximately 8 weeks
Secondary outcomes (1)
DEXA, insulin sensitivity and energy expenditure changes due to dietary intervention
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2008 (estimated)
- Study startSep 2007
- Primary completion12 Oct 2012
- Study completion12 Oct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Touro University, American Diabetes Association
- Responsible party
- Sponsor
- Investigators
- Jean-Marc Schwarz, PhD, Principal investigator, Touro University and UCSF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00714129
- Sponsor's protocol ID
- R01DK078133-01
- Other IDs
- NIH R01DK078133-01A1, ADA 1-08-CR-56
- Acronym
- LINC
- Status last verified
- Feb 2020
- First submitted
- 9 Jul 2008
- Last updated
- 17 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- De Novo Lipogenesis, Lipid and Carbohydrate Metabolism in Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT00714129
- Acronym / sponsor ID
- LINC / R01DK078133-01
- Conditions
- Non-alcoholic Fatty Liver Disease, Diabetes
- Keywords
- Steatosis, Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Touro University, American Diabetes Association
- Study start
- Sep 2007
- Primary completion
- 12 Oct 2012 (actual)
- Study completion
- 12 Oct 2012 (actual)
- First posted
- 14 Jul 2008 (estimated)
- 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.
The worldwide epidemic of obesity is paralleled with increased cases of non-alcoholic liver disease (liver fat accumulation) and diabetes. Fat belongs in the adipose tissue, and if excess fat accumulates in the liver or muscle, these tissues cannot use sugar efficiently. It has been discovered that when large quantities of fructose (a sugar present in soft drinks) are consumed, the conversion of carbohydrate (CHO) to fat in the liver increases.
We hypothesize that: 1) subjects with fatty liver have a higher CHO uptake and conversion to fat in their liver when compared to matched control subjects with normal liver fat content; and that: 2) when subjects with fatty liver are fed a diet limiting fructose and simple sugars will decrease their liver CHO fat content. This reduction in liver fat will normalize the way the liver responds to sugar and insulin, reversing the pre-diabetic state.
The measurement of these parameters will be done using state-of-the-art techniques such as safe non-radioactive isotope tracers and non-invasive magnetic resonance spectroscopy.
For more information, please call 415-206-5532 for a phone screening
Detailed description
Non-alcoholic fatty liver disease (NAFLD) is the most common liver ailment in developed countries. Fatty liver - steatosis - affects up to one third of the population. Its prevalence is rising and seems to parallel the global increase in obesity and type-2 diabetes. The etiology of NAFLD in humans is not well understood. We propose that the hepatic conversion of carbohydrates (CHO) to lipids (de novo lipogenesis, DNL) is a key factor in the accumulation of excess liver fat and the accompanying dyslipidemia and hepatic insulin resistance; and that suppressing DNL by diet will reduce liver fat and improve both lipid and carbohydrate metabolism in patients with steatosis. These hypotheses are based on studies in which we and others have established that fractional hepatic DNL can vary dramatically depending on the diet and/or health status of a subject; and, in particular, that dietary fructose is a potent lipogenic stimulus. In this proposal we will perform CRC-based studies to compare the rates of DNL and very low density lipoprotein (VLDL) kinetics in steatotic and matched non-steatotic controls and evaluate their relationship to lipid profiles and hepatic and whole-body insulin resistance and overall carbohydrate metabolism (Aim1). The steatotic individuals whose habitual intake of fructose and other simple sugars exceeds 15% of total energy intake will then be randomized to consume one of two low-fat diets that differ only in CHO type to determine whether diet-induced changes in DNL affect liver fat flux and content and hepatic, whole-body insulin sensitivity, and overall carbohydrate metabolism (Aim 2). We hypothesize that a diet that is rich in complex CHO will achieve greater decreases in DNL and liver fat than one that contains typical amounts of simple CHO, including fructose. This dietary intervention study includes a 6-week 25% energy restriction outpatient phase to promote moderate weight loss and improve insulin sensitivity, followed by a two weeks weight maintenance with the last 4 days as an inpatient stay during which all of the studies performed at baseline (Aim 1) will be repeated. State-of-the-art stable isotope techniques will be used to assess hepatic DNL, apoB100 turnover, VLDL-triglyceride (TG) fluxes, and lipolysis under fasting and fed conditions. Hepatic and extra-hepatic insulin sensitivity will be measured using hyperinsulinemic-euglycemic clamps and stable isotope studies of endogenous glucose production and glycogen flux. Liver and muscle fat will be measured by proton magnetic resonance spectroscopy (MRS), visceral fat by magnetic resonance imaging (MRI), and whole-body composition by dual-energy X-ray absorptiometry (DEXA). These studies will allow us to evaluate the importance of DNL as a mechanism modulating liver fat content and flux, and the significance of CHO quality in dietary guidance for steatotic patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Dietary intervention (calorie restricted diet)Weight loss diet - normal diet |
| 2 | Experimental | Other: Dietary intervention (calorie restricted diet)Weight loss diet - low in simple sugars (specifically fructose) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- In the steatotic subjects, steatosis will be diagnosed by MRS or liver biopsy in which >33% of the hepatocytes will contain fat. Non-steatotic controls will not have biopsies since they are not medically warranted; thus, to ensure they do not have steatosis they will undergo MRS during screening and have a total lipid: unsuppressed water < 0.05.
Key exclusion criteria (11 listed)
- Habitual consumption of alcohol > 20 g/day for men and 10 g/day for women
- Confirmed HIV-1 infection, Hgb <13 g/dL for males and <12 g/dL for females
- Abnormal hepatitis B or C serology
- Diabetes or current use of any antidiabetic or hypolipidemic agents
- Presence of metal-containing substances in the body (e.g. a fragment in the eye, aneurysm clips, ear implants, spinal nerve stimulators or a pacemaker)
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 (calorie restricted diet)Participants in Aim 2 will receive a calorie restricted diet. This group will receive all their food for approximately 8 weeks which is the similar composition of their current diet. | Other | 1 |
| Dietary intervention (calorie restricted diet)Participants in Aim 2 will receive a calorie restricted diet. This group will receive all their food for approximately 8 weeks which is lower in simple sugars, specifically fructose. | Other | 2 |
Primary outcome
Stable isotopic and magnetic resonance measures to determine the changes in lipid and carbohydrate metabolism after dietary intervention
Time frame: approximately 8 weeks
1 secondary outcome
DEXA, insulin sensitivity and energy expenditure changes due to dietary intervention
Time frame: 8 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 17 Feb 2020.
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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.
Jean-Marc Schwarz, PhD principal investigator
Touro University and UCSF
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 (calorie restricted diet) in people with Non-alcoholic Fatty Liver Disease and Diabetes, run by University of California, San Francisco at 1 site in United States.
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 1 inclusion and 11 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 17 Feb 2020. 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 United States. 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?
Stable isotopic and magnetic resonance measures to determine the changes in lipid and carbohydrate metabolism after dietary intervention (time frame: approximately 8 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 17 Feb 2020.