Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It encompasses both a fatty liver and nonalcoholic steatohepatitis (NASH). The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to the clinical features, risk factors, pathogenesis, natural history and treatment of NAFLD in children and adults. Encouraged by its success, the NIDDK has issued RFA-DK-08-505 whose objective is to continue the NASH CRN for five more years. The objectives of the NASH CRN during the next five years are: (1) to successfully complete three network wide studies initiated during the initial funding period. These include an observational longitudinal study of NAFLD in adults and children (NAFLD database study, n=1215), a randomized double blind controlled trial of pioglitazone or vitamin E vs. placebo (PIVENS) (n=247) in nondiabetic adults with NASH, and a randomized double blind controlled trial of metformin or vitamin E vs. placebo (TONIC) (n= 173). These studies are fully enrolled. The NAFLD database will be amended to allow further follow up of enrolled subjects, perform liver biopsies on selected subjects and add carefully defined controls as well as additional subjects with NAFLD. The rationale for this is to definitively evaluate the natural history of the disease, develop and validate biomarkers and complete ancillary studies that are still underpowered despite use of the current database, (2) to complete the numerous pilot and ancillary studies that have been initiated, (3) to perform additional therapeutic trials in adults and children with NASH. The specific studies will be based on proposals received from individual centers that are approved by the NASH CRN steering committee and the NIDDK for which funding is available, and (4) to conduct new ancillary studies proposed by individual centers. Two studies are proposed by this center: (a) to validate the metabolomic signature of NASH. Preliminary studies have identified a distinct lipidomic signature of NASH, (b) to perform a randomized controlled trial of laparoscopic adjustable band gastroplasty (LABG) for adults with NASH who have a BMI between 30-45. This trial will test the hypothesis that LABG is a safe and effective treatment of NASH. Together, all of these studies are directly aligned with the NIH liver action plan for NAFLD. Public Health Relevance: (provided by the applicant): NAFLD and NASH are important health problems and their incidence is expected to increase. During the initial funding period, the CRN has made important contributions to the field of NAFLD and NASH, however there remain numerous unanswered questions. During the next funding period, the CRN will continue to investigate risk factors, clinical aspects, natural history and optimal treatment for NASH and associated conditions

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK061731-11
Application #
8301758
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Doo, Edward
Project Start
2002-05-20
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
11
Fiscal Year
2012
Total Cost
$633,846
Indirect Cost
$173,215
Name
Virginia Commonwealth University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
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