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Fatty LiverNCT00252499

Insulin Resistance in Non-alcoholic Fatty Liver Disease

A study testing rosiglitazone and fenofibrate in people with Fatty Liver and Insulin Resistance, run by US Department of Veterans Affairs at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to determine whether nonalcoholic fatty liver disease (NAFLD) is associated with altered peripheral and hepatic insulin sensitivity and to investigate potential mechanisms underlying insulin resistance in NAFLD by determining associations between hepatic and peripheral insulin sensitivity… Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Fatty Liver, Insulin Resistance
What is being tested?
rosiglitazone and fenofibrate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
13 participants
Where
1 siteUnited States
Study dates
Oct 2005to Aug 2010
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 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age 18-80 years old Controls:
  • otherwise healthy Case subjects: NAFLD on liver biopsy within the past 3 years or presumed NAFLD with otherwise unexplained elevated ALT and fatty liver by CT or ultrasound
  • Able to comply with taking 3 pills a day for 6 months and follow-up safety visits

Who cannot join

  • Controls:
  • history or evidence of hepatic steatosis
  • Cases:
  • Cirrhosis on liver biopsy or by clinical exam or fibrosis score
  • Causes of liver dysfunction other than NASH
  • Use of medications associated with hepatic steatosis:
Show all 37Show fewer
  • glucocorticoids
  • estrogens
  • tamoxifen
  • amiodarone
  • accutane
  • sertraline
  • Use of medications that cause insulin resistance:
  • niacin
  • glucocorticoids
  • anti-HIV drugs or atypical antipsychotics
  • Use of lipid-lowering medications except stable dose statin
  • Use of anti-NASH drugs such as:
  • ursodeoxycholic acid
  • betaine milk thistle
  • Use of coumadin
  • Use of nitrates
  • Significant alcohol consumption:
  • Average >20 grams/day
  • In subjects with diabetes
  • a HbA1c >7.5% or use of insulin
  • metformin
  • rosiglitazone or pioglitazone
  • Liver transaminases:
  • Cases: ALT >5x upper limit of normal
  • Controls: ALT or AST above the normal range
  • Iron saturation >50%
  • Creatinine >1.5 mg/dl for men and >1.4 mg/dl for women
  • Hematocrit <33%
  • Pregnancy or lactation
  • Significant weight loss within the past 6 months for controls, or since the liver biopsy for case subjects, history of significant coronary artery disease or congestive heart failure
  • Retinopathy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • VA Puget Sound Health Care System, Seattle

    Seattle, Washington, 98108

Other trials in United States

About this study

The purpose of this study is to determine whether nonalcoholic fatty liver disease (NAFLD) is associated with altered peripheral and hepatic insulin sensitivity and to investigate potential mechanisms underlying insulin resistance in NAFLD by determining associations between hepatic and peripheral insulin sensitivity, hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose metabolism, beta-cell function and body fat distribution.

Read the detailed description

NAFLD and nonalcoholic steatohepatitis (NASH) are common liver disorders that are strongly associated with obesity, type 2 diabetes and dyslipidemia. The underlying pathophysiology of fatty infiltration of the liver is thought to be related to insulin resistance, which is an almost universal finding in patients with NAFLD. It is also possible that fat infiltration and inflammation in the liver may impair insulin sensitivity, either locally in the liver, or peripherally via the actions of inflammatory cytokines. We hypothesize that insulin resistance is a major causal factor leading to fat deposition in the liver and NAFLD, and thus interventions aimed at improving insulin sensitivity will result in a reduction of hepatic inflammation and steatosis.

Specific Aim 1: To determine in a cross-sectional study whether NAFLD is associated with altered peripheral and hepatic insulin sensitivity and to study their relationships with hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose metabolism, -cell function and body fat distribution. Specific Aim 2: To determine in a 6 month placebo-controlled double-blinded treatment study if treatment with rosiglitazone, an insulin sensitizer, or fenofibrate, a triglyceride lowering agent, will improve both hepatic as well as peripheral insulin sensitivity and thereby improve hepatic steatosis and inflammation in subjects with NAFLD.

The results of the proposed study will have important implications for our understanding of the mechanisms underlying insulin resistance and abnormalities in lipid and glucose metabolism in subjects with NAFLD and for the design of future studies aimed at the prevention and treatment of this condition.

Being tested
rosiglitazone, fenofibrate, placebo for rosiglitazone, placebo for fenofibrate
Keywords
beta cell function, fenofibrate, non-alcoholic steatohepatitis, rosiglitazone, insulin sensitivity
Medical subject headings
Fatty Liver, Insulin Resistance, Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rosiglitazoneDrug

    PPAR-gamma agonist, insulin sensitizer

  • fenofibrateDrug

    PPAR-alpha agonist, reduces triglycerides

  • placebo for rosiglitazoneDrug

    placebo tablets that are matched to look like rosiglitazone

  • placebo for fenofibrateDrug

    placebo matched to look like fenofibrate tablets

Study groups in NCT00252499
Study groupRoleWhat they receive
Placebo ArmPlacebo comparatormatching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd
Receives: Drug: placebo for rosiglitazone; Drug: placebo for fenofibrate
Rosiglitazone ArmExperimentalrosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd
Receives: Drug: rosiglitazone; Drug: placebo for fenofibrate
Fenofibrate ArmExperimentalmicronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Receives: Drug: fenofibrate; Drug: placebo for rosiglitazone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Liver/Spleen Ratio at 6 Months

    Liver fat was estimated by non-contrast CT scan measuring the density ratio between the liver and spleen by Hounsfield units (liver/spleen ratio), which has been previously correlated with liver fat quantification by magnetic resonance spectroscopy.Ten separate measurements equally distributed throughout the liver and spleen were obtained and the Hounsfield units averaged. In subjects with more than one slice through the liver and spleen, the values for all slices were averaged.

    Measured: 6 months

Secondary outcomes (5)

  1. Change in Alanine Aminotransferase (ALT) Levels From Baseline to 6 Months

    Measured: 6 months

  2. Change in the Liver Spleen Ratio by CT Scan From Baseline to 6 Months as a Measure of Fat in the Liver

    Measured: 6 months

  3. Change in Peripheral Insulin Sensitivity From Baseline to 6 Months

    A two-step stable isotope labeled, hyperinsulinemic-euglycemic clamp procedure was performed with a low dose insulin infusion (20 mU/m2/min) for 3 hours followed by a primed high dose insulin infusion (160 mU/m2/min x 5 minutes then 80 mU/m2/min) for two hours. D20 was infused and adjusted to maintain the blood glucose at 90 mg/dl. Samples for glucose, insulin and 6,6 2d glucose were drawn every 15 minutes during the final half hour of the basal, low dose and high dose insulin periods. Whole body insulin sensitivity was calculated as the rate of glucose disposal (Rd)/lean body mass during the high dose insulin infusion.

    Measured: 6 months

  4. Changes in Intra-abdominal Fat Area From Baseline to 6 Months

    Unenhanced CT scan images were obtained on a General Electric Discovery HD750 CT scanner. Intra-abdominal (IAF) areas were measured at the top of the iliac crest and quantified using the Tomovision program (SliceOMatic V4.3) by one trained technologist.

    Measured: 6 months

  5. Change in Hepatic Insulin Sensitivity From Baseline to 6 Months

    Hepatic insulin sensitivity was determined as the percent suppression of endogenous glucose production (EGP) at the end of the low dose insulin clamp.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2005 (estimated)
  2. Study startOct 2005
  3. Primary completionAug 2010
  4. Study completionAug 2010

Why it stopped: Protocol drug change required new clinicaltrails.gov entry

Resources

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00252499
Sponsor's protocol ID
CDA-2-044-08S
Status last verified
Aug 2014
First submitted
9 Nov 2005
Last updated
20 Aug 2014
Data monitoring committee
No

Publications

  • Utzschneider KM, Largajolli A, Bertoldo A, Marcovina S, Nelson JE, Yeh MM, Kowdley KV, Kahn SE. Serum ferritin is associated with non-alcoholic fatty liver disease and decreased Beta-cell function in non-diabetic men and women. J Diabetes Complications. 2014 Mar-Apr;28(2):177-84. doi: 10.1016/j.jdiacomp.2013.11.007. Epub 2013 Nov 26.

    PubMed 24360972

  • Kratz M, Marcovina S, Nelson JE, Yeh MM, Kowdley KV, Callahan HS, Song X, Di C, Utzschneider KM. Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not beta-cell function in humans. Am J Clin Nutr. 2014 Jun;99(6):1385-96. doi: 10.3945/ajcn.113.075457. Epub 2014 Apr 16.

    PubMed 24740208

Questions about this trial

What is this clinical trial studying?

A study testing rosiglitazone and fenofibrate in people with Fatty Liver and Insulin Resistance, run by US Department of Veterans Affairs 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 3 inclusion and 37 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: stopped early, as of the sponsor's last update on 20 Aug 2014. 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 11 Apr 2014). 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?

Liver/Spleen Ratio at 6 Months (time frame: 6 months). 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 NCT00252499, which also lists 2 linked publications.

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 20 Aug 2014.

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