Non-alcoholic Fatty Liver DiseaseNCT00262964
Obesity and Nonalcoholic Fatty Liver Disease
A study testing Niacin and fenofibrate in people with Non-alcoholic Fatty Liver Disease, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The primary goal of this study is to provide a better understanding of: 1) the pathogenesis and pathophysiology of non-alcoholic fatty liver disease (NAFLD) in obese subjects, and 2) the effect of marked weight loss on the histologic and metabolic abnormalities associated with NAFLD. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Niacin and fenofibrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Dec 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All
- 18 - 45 years old
- Class I obesity, i.e. Body Mass Index (BMI) between 30 and 45.
- weight less than 300 lbs.
Who cannot join
- Active or previous infection with hepatitis B or C, as well as other liver disease.
- History of alcohol abuse
- Diabetes
- Medications that cause liver damage or steatosis.
- Women who are pregnant or lactating.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
The primary goal of this study is to provide a better understanding of: 1) the pathogenesis and pathophysiology of non-alcoholic fatty liver disease (NAFLD) in obese subjects, and 2) the effect of marked weight loss on the histologic and metabolic abnormalities associated with NAFLD. The following hypotheses will be tested:
- obesity causes hepatic fat accumulation because of excessive fatty acid release from fat tissue and increased free fatty acid availability,
- increased hepatic (liver) fat content causes insulin-resistant glucose (sugar) production by the liver and altered liver protein synthesis,
- increased hepatic fat content causes increased lipid (fat) peroxidation, hepatic inflammation, necrosis and fibrosis, and
- marked weight loss improves NAFLD once patients are weight stable.
Read the detailed description
Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD), which represents a spectrum of liver diseases. NAFLD is a major health problem in the US because of its high prevalence and causal relationship with serious liver abnormalities. However, the mechanism(s)responsible for developing NAFLD in obese persons and the effects on liver function are not known. This gap in knowledge has made it difficult to identify effective therapy. The results from these studies will lay the groundwork for the development of novel therapeutic interventions for NAFLD in obese patients.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- Niacin, fenofibrate, placebo
- Keywords
- non-alcoholic fatty liver disease, obesity, fatty liver disease
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiacinDrug
Also called niaspan
Subjects randomized to Niacin therapy will be treated with Niacin at night for 16 wks to reduce plasma free fatty acid concentrations. The dose of medication will be gradually increased: 500 mg/day during week 1, 1000 mg/day during week 2, 1500 mg/day during week 3, and 2000mg/day during weeks 4-16.
fenofibrateDrug
Also called Tricor
Subjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks.
placeboDrug
Subjects randomized to placebo will be treated with one placebo pill per day for eight weeks.
| Study group | Role | What they receive |
|---|---|---|
| NAFLD-Niacin | Experimental | Subjects, having previously diagnosed with NAFLD, were given Niacin for 16 weeks. The dosage was 500mg/day for week 1, 1000mg/day for week 2, 1500mg/day for week three and 2000mg/day for weeks 4 through 16. Receives: Drug: Niacin |
| Control | No intervention | Subjects were found to have intrahepatic triglyceride levels below the threshold for Non-Alcoholic Fatty Liver Disease (NAFLD). For this study that threshold was set at 10% intrahepatic triglyceride content as determined by magnetic resonance spectroscopy. These control subjects did not participate in any intervention. Only baseline features were characterized for this arm. |
| NAFLD-fenofibrate | Experimental | Subjects diagnosed with NAFLD were randomized to fenofibrate, an oral medication, nightly for eight weeks. Subjects will be given a dose of 200mg/day. Receives: Drug: fenofibrate |
| NAFLD-placebo | Placebo comparator | These subjects were diagnosed with Non-Alcoholic Fatty Liver Disease (NAFLD) and received an 8 week course of a placebo pill. Their baseline characteristics were averaged into the overall NAFLD baseline characteristics along with the baseline data for the two intervention groups. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic Insulin Sensitivity Index (HISI)
Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index(HISI) is the reciprocal of glucose rate of appearance [10000/(μmol/min)] multiplied by insulin concentration[mU/L]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.
Measured: baseline cross-sectional data
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
A precise measure of the ability of insulin to stimulate glucose uptake by skeletal muscle. Skeletal muscle insulin sensitivity, measured as the increase from baseline in skeletal muscle glucose uptake during insulin infusion(percentage)as part of a nine hour euglycemic hyperinsulinemic clamp study.
Measured: baseline cross-sectional data pre and post nine hour euglycemic clamp
Adipose Tissue Insulin Sensitivity
The ability of insulin to suppress the release of fatty acids from adipose tissue: Adipose tissue insulin sensitivity, measured as the suppression from baseline of free fatty acid release from adipose tissue (lipolysis) during insulin infusion as part of a nine hour euglycemic hyperinsulinemic clamp study.
Measured: baseline cross-sectional data pre and post nine hour euglycemic clamp
Hepatic Fat Content for Fenofibrate and Niacin Groups
Hepatic fat content as measured by magnetic resonance spectroscopy. A PRESS sequence was used. The results from three 10 cubic centimeter voxels positioned within the liver were averaged. The measure is a ratio of triglyceride signal to total signal.
Measured: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
The baseline and post-treatment measures of adipose tissue insulin sensitivity (ATIS) were compared. ATIS at both timepoints is the suppression from fasting levels of free fatty acid release from adipose tissue (lipolysis) during an insulin infusion as part of a euglycemic clamp study. It is the percent decrease from time zero to the end of the nine hour euglycemic hyperinsulinemic clamp
Measured: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in Skeletal Muscle Insulin Sensitivity
Changes in skeletal muscle insulin sensitivity (SMIS). SMIS was measured as the increase in skeletal muscle glucose uptake from time zero to the end of a nine hour euglycemic clamp and insulin infusion study. This increase is the percentage change from time zero to end of insulin infusion at nine hours.
Measured: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in Hepatic Insulin Sensitivity Index
Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index (HISI) is measured as the reciprocal of glucose rate of appearance [10000/(μmol/min)] multiplied by insulin concentration[mU/L]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.
Measured: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Secondary outcomes (5)
Very Low Density Lipoprotein - Triglyceride Production Rate
Very low density lipoprotein triglyceride (VLDL-TG) production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute (μmol/L/min).
Measured: baseline cross-sectional data
Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate
VLDL-apolipoprotein B (apoB) concentrations were measured as part of a VLDL metabolism study utilizing stable isotope tracers. VLDL apoB production rate, a measure of hepatic secretion of VLDL-apolipoproteinB-100 per liter of plasma per minute.
Measured: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in VLDL-Tg Clearance Rate
Very low density lipoprotein triglyceride (VLDL-Tg) clearance rate, a measure of VLDL-triglyceride removal from plasma per minute.
Measured: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in VLDL-Tg Production Rate
VLDL-TG production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute.
Measured: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)
Measured: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2005 (estimated)
- Study startOct 2004
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00262964
- Sponsor's protocol ID
- DK37948
- Other IDs
- R01DK037948
- Status last verified
- Jun 2018
- First submitted
- 6 Dec 2005
- Last updated
- 11 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Obesity and Nonalcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT00262964
- Acronym / sponsor ID
- DK37948
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- non-alcoholic fatty liver disease, obesity, fatty liver disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Oct 2004
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 7 Dec 2005 (estimated)
- Results
- Posted 28 Jun 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary goal of this study is to provide a better understanding of: 1) the pathogenesis and pathophysiology of non-alcoholic fatty liver disease (NAFLD) in obese subjects, and 2) the effect of marked weight loss on the histologic and metabolic abnormalities associated with NAFLD. The following hypotheses will be tested:
- obesity causes hepatic fat accumulation because of excessive fatty acid release from fat tissue and increased free fatty acid availability,
- increased hepatic (liver) fat content causes insulin-resistant glucose (sugar) production by the liver and altered liver protein synthesis,
- increased hepatic fat content causes increased lipid (fat) peroxidation, hepatic inflammation, necrosis and fibrosis, and
- marked weight loss improves NAFLD once patients are weight stable.
Detailed description
Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD), which represents a spectrum of liver diseases. NAFLD is a major health problem in the US because of its high prevalence and causal relationship with serious liver abnormalities. However, the mechanism(s)responsible for developing NAFLD in obese persons and the effects on liver function are not known. This gap in knowledge has made it difficult to identify effective therapy. The results from these studies will lay the groundwork for the development of novel therapeutic interventions for NAFLD in obese patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NAFLD-Niacin | Experimental | Drug: NiacinSubjects, having previously diagnosed with NAFLD, were given Niacin for 16 weeks. The dosage was 500mg/day for week 1, 1000mg/day for week 2, 1500mg/day for week three and 2000mg/day for weeks 4 through 16. |
| Control | No intervention | –Subjects were found to have intrahepatic triglyceride levels below the threshold for Non-Alcoholic Fatty Liver Disease (NAFLD). For this study that threshold was set at 10% intrahepatic triglyceride content as determined by magnetic resonance spectroscopy. These control subjects did not participate in any intervention. Only baseline features were characterized for this arm. |
| NAFLD-fenofibrate | Experimental | Drug: fenofibrateSubjects diagnosed with NAFLD were randomized to fenofibrate, an oral medication, nightly for eight weeks. Subjects will be given a dose of 200mg/day. |
| NAFLD-placebo | Placebo comparator | Drug: placeboThese subjects were diagnosed with Non-Alcoholic Fatty Liver Disease (NAFLD) and received an 8 week course of a placebo pill. Their baseline characteristics were averaged into the overall NAFLD baseline characteristics along with the baseline data for the two intervention groups. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- All
- 18 - 45 years old
- Class I obesity, i.e. Body Mass Index (BMI) between 30 and 45.
- weight less than 300 lbs.
Key exclusion criteria (5 listed)
- Active or previous infection with hepatitis B or C, as well as other liver disease.
- History of alcohol abuse
- Diabetes
- Medications that cause liver damage or steatosis.
- Women who are pregnant or lactating.
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 |
|---|---|---|
| NiacinAlso: niaspanSubjects randomized to Niacin therapy will be treated with Niacin at night for 16 wks to reduce plasma free fatty acid concentrations. The dose of medication will be gradually increased: 500 mg/day during week 1, 1000 mg/day during week 2, 1500 mg/day during week 3, and 2000mg/day during weeks 4-16. | Drug | NAFLD-Niacin |
| fenofibrateAlso: TricorSubjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks. | Drug | NAFLD-fenofibrate |
| placeboSubjects randomized to placebo will be treated with one placebo pill per day for eight weeks. | Drug | NAFLD-placebo |
Primary outcome
Hepatic Insulin Sensitivity Index (HISI)
Time frame: baseline cross-sectional data
Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index(HISI) is the reciprocal of glucose rate of appearance [10000/(μmol/min)] multiplied by insulin concentration[mU/L]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
Time frame: baseline cross-sectional data pre and post nine hour euglycemic clamp
A precise measure of the ability of insulin to stimulate glucose uptake by skeletal muscle. Skeletal muscle insulin sensitivity, measured as the increase from baseline in skeletal muscle glucose uptake during insulin infusion(percentage)as part of a nine hour euglycemic hyperinsulinemic clamp study.
Adipose Tissue Insulin Sensitivity
Time frame: baseline cross-sectional data pre and post nine hour euglycemic clamp
The ability of insulin to suppress the release of fatty acids from adipose tissue: Adipose tissue insulin sensitivity, measured as the suppression from baseline of free fatty acid release from adipose tissue (lipolysis) during insulin infusion as part of a nine hour euglycemic hyperinsulinemic clamp study.
Hepatic Fat Content for Fenofibrate and Niacin Groups
Time frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Hepatic fat content as measured by magnetic resonance spectroscopy. A PRESS sequence was used. The results from three 10 cubic centimeter voxels positioned within the liver were averaged. The measure is a ratio of triglyceride signal to total signal.
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
Time frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
The baseline and post-treatment measures of adipose tissue insulin sensitivity (ATIS) were compared. ATIS at both timepoints is the suppression from fasting levels of free fatty acid release from adipose tissue (lipolysis) during an insulin infusion as part of a euglycemic clamp study. It is the percent decrease from time zero to the end of the nine hour euglycemic hyperinsulinemic clamp
Change From Baseline in Skeletal Muscle Insulin Sensitivity
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Changes in skeletal muscle insulin sensitivity (SMIS). SMIS was measured as the increase in skeletal muscle glucose uptake from time zero to the end of a nine hour euglycemic clamp and insulin infusion study. This increase is the percentage change from time zero to end of insulin infusion at nine hours.
Change From Baseline in Hepatic Insulin Sensitivity Index
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index (HISI) is measured as the reciprocal of glucose rate of appearance [10000/(μmol/min)] multiplied by insulin concentration[mU/L]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.
5 secondary outcomes
Very Low Density Lipoprotein - Triglyceride Production Rate
Time frame: baseline cross-sectional data
Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate
Time frame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in VLDL-Tg Clearance Rate
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in VLDL-Tg Production Rate
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Non-alcoholic Fatty Liver Disease
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
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.
Samuel Klein, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Niacin and fenofibrate in people with Non-alcoholic Fatty Liver Disease, run by Washington University School of Medicine 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 4 inclusion and 5 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 11 Jul 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 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 28 Jun 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hepatic Insulin Sensitivity Index (HISI) (time frame: baseline cross-sectional data). The study lists 7 primary outcomes in all. 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 11 Jul 2018.