NCT00252499

Brief 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, hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose metabolism, beta-cell function and body fat distribution.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Oct 2005

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2005

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

November 9, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 11, 2005

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
3.7 years until next milestone

Results Posted

Study results publicly available

April 11, 2014

Completed
Last Updated

August 20, 2014

Status Verified

August 1, 2014

Enrollment Period

4.8 years

First QC Date

November 9, 2005

Results QC Date

November 12, 2013

Last Update Submit

August 18, 2014

Conditions

Keywords

beta cell functionfenofibratenon-alcoholic steatohepatitisrosiglitazoneinsulin sensitivity

Outcome Measures

Primary Outcomes (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.

    6 months

Secondary Outcomes (5)

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

    6 months

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

    6 months

  • Change in Peripheral Insulin Sensitivity From Baseline to 6 Months

    6 months

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

    6 months

  • Change in Hepatic Insulin Sensitivity From Baseline to 6 Months

    6 months

Study Arms (3)

Placebo Arm

PLACEBO COMPARATOR

matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd

Drug: placebo for rosiglitazoneDrug: placebo for fenofibrate

Rosiglitazone Arm

EXPERIMENTAL

rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd

Drug: rosiglitazoneDrug: placebo for fenofibrate

Fenofibrate Arm

EXPERIMENTAL

micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid

Drug: fenofibrateDrug: placebo for rosiglitazone

Interventions

PPAR-gamma agonist, insulin sensitizer

Rosiglitazone Arm

PPAR-alpha agonist, reduces triglycerides

Fenofibrate Arm

placebo tablets that are matched to look like rosiglitazone

Fenofibrate ArmPlacebo Arm

placebo matched to look like fenofibrate tablets

Placebo ArmRosiglitazone Arm

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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:
  • glucocorticoids
  • estrogens
  • tamoxifen
  • amiodarone
  • accutane
  • sertraline
  • Use of medications that cause insulin resistance:
  • niacin
  • glucocorticoids
  • +22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VA Puget Sound Health Care System, Seattle

Seattle, Washington, 98108, United States

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Fatty LiverInsulin ResistanceNon-alcoholic Fatty Liver Disease

Interventions

RosiglitazoneFenofibrate

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFibric AcidsIsobutyratesButyratesAcids, AcyclicCarboxylic AcidsPhenyl EthersEthersBenzophenonesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPhenolsKetones

Limitations and Caveats

Due to recruitment difficulties and concerns about the safety of thiazolidinediones, recruitment was stopped without achieving adequate sample size (16/arm). Thus, no definitive conclusions can be made about the study medications.

Results Point of Contact

Title
Kristina Utzschneider, MD
Organization
VA Puget Sound Health Care System

Study Officials

  • Kristina Marie Utzschneider, MD

    VA Puget Sound Health Care System, Seattle

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2005

First Posted

November 11, 2005

Study Start

October 1, 2005

Primary Completion

August 1, 2010

Study Completion

August 1, 2010

Last Updated

August 20, 2014

Results First Posted

April 11, 2014

Record last verified: 2014-08

Locations