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Fatty LiverNCT01289639

Insulin Resistance in Non-alcoholic Fatty Liver Disease

A study testing fenofibrate and pioglitazone in people with Fatty Liver, run by VA Office of Research and Development 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 study is designed to investigate the relationship between insulin resistance and non-alcoholic fatty liver disease (NAFLD) and to investigate potential mechanisms underlying insulin resistance in NAFLD by determining associations between hepatic and peripheral insulin sensitivity, hepatic steatosis, dyslipidemia… 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
What is being tested?
fenofibrate and pioglitazone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
11 participants
Where
1 siteUnited States
Study dates
Oct 2005to Aug 2014
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

  • Control subjects: nl liver enzymes and no history of liver disease Case subjects: NAFLD on liver biopsy within the past 3 years or presumed NAFLD with otherwise unexplained elevated alanine aminotransferase (ALT) and fatty liver by computerized tomography (CT) scan or ultrasound
  • Able to comply with taking 1 pill a day for 6 months and follow-up safety visits

Who cannot join

  • 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:
  • glucocorticoids
  • estrogens
  • tamoxifen
Show all 26Show fewer
  • 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 hemoglobin A1c (HbA1c) >7.5% or use of insulin, metformin, rosiglitazone or pioglitazone
  • Liver transaminases: ALT >5x upper limit of normal,
  • 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 or since the liver biopsy
  • 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

Official title: Insulin Resistance in Non-alcoholic Fatty Liver Disease (Protocol Drug Change From Project Career Development Award (CDA)-2-044-08S)

The study is designed to investigate the relationship between insulin resistance and non-alcoholic fatty liver disease (NAFLD) 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, beta-cell function and body fat distribution. Specific Aim 2: To determine in a 6 month placebo-controlled double-blinded treatment study if treatment with pioglitazone, 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.

Conditions
Fatty Liver
Being tested
fenofibrate, pioglitazone, placebo
Keywords
non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, insulin resistance, pioglitazone, fenofibrate
Medical subject headings
Fatty Liver, 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.

  • fenofibrateDrug

    Also called micronized fenofibrate

    micronized fenofibrate 200 mg 1 po qd

  • pioglitazoneDrug

    Also called Actos

    pioglitazone 30 mg po qd

  • placeboDrug

    placebo 1 capsule po qd

Study groups in NCT01289639
Study groupRoleWhat they receive
PlaceboPlacebo comparatormatching placebo 1 po qd
Receives: Drug: placebo
FenofibrateExperimentalmicronized fenofibrate 200 mg 1 po qd
Receives: Drug: fenofibrate
PioglitazoneExperimentalpioglitazone 30 mg po qd
Receives: Drug: pioglitazone

What is being measured

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

  1. Liver/Spleen Ratio Measured as the Ratio in Hounsfield Units Between the Liver and the Spleen on Computed Tomography (CT) Scan

    Measured: 6 months

Secondary outcomes (5)

  1. Change in Alanine Aminotransferase (ALT) Levels

    Measured: 0-6 months

  2. Change in Liver/Spleen Ratio Measure by the Density Ratio in Hounsfield Units Between the Liver and the Spleen by CT

    Measured: 0-6 months

  3. Change in Peripheral Insulin Sensitivity

    Change in the rate of glucose disposal (Rd) during the low dose clamp. During a clamp procedure, insulin is infused at a dose based on body size and a glucose solution is infused and the rate adjusted every 5 minutes based on a blood glucose reading to maintain the blood glucose stable at 90 mg/dl (normal level). Using glucose isotopes and the rate of the glucose infusion, we are then able to calculate how much glucose the liver is producing and how much glucose is being taken up into tissues. This provides a measure of insulin sensitivity.

    Measured: 0-6 months

  4. Change in Intra-abdominal Fat Area by CT Scan

    Measured: 0-6 months

  5. Change in Hepatic Insulin Sensitivity

    Hepatic insulin sensitivity was determined using stable glucose isotope measurements during the low dose hyperinsulinemic euglycemic clamp to determine the rate of endogenous glucose production in the fasting state and in response to a low dose glucose infusion. The ability of insulin to suppress glucose, which is mainly produced by the liver, thus provides a measure of hepatic insulin sensitivity and is expressed as a percentage of the basal state. Change in the ability of low dose insulin to suppress endogenous glucose production during a labeled hyperinsulinemic euglycemic clamp.

    Measured: 0-6 months

Timeline

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

  1. First posted4 Feb 2011 (estimated)
  2. Study startOct 2005
  3. Primary completionAug 2013
  4. Study completionAug 2014

Why it stopped: Low recruitment in intervention study. Baseline data published.

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
Double blind
Who is masked
Participant, Investigator
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01289639
Sponsor's protocol ID
CDA-2-044-08S-2
Status last verified
Jul 2017
First submitted
21 Jan 2011
Last updated
17 Aug 2017
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 fenofibrate and pioglitazone in people with Fatty Liver, run by VA Office of Research and Development 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 2 inclusion and 26 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 17 Aug 2017. 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 20 Oct 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 Measured as the Ratio in Hounsfield Units Between the Liver and the Spleen on Computed Tomography (CT) Scan (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 NCT01289639, 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 17 Aug 2017.

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