NASH CLINICAL RESEARCH NETWORK LAUNCHES NEW TRIAL FOR TREATMENT OF LIVER DISEASE

[Guest guest]

U.S. Department of Health and Human ServicesNATIONAL INSTITUTES OF HEALTHNIH NewsNational Institute of Diabetesand Digestive and Kidney Diseases (NIDDK)http://www.niddk.nih.gov/FOR IMMEDIATE RELEASEFriday, April 1, 2005CONTACT: Curtis301-496-3583lesliecurtis@...NASH CLINICAL RESEARCH NETWORK LAUNCHES NEW TRIAL FOR TREATMENT OF LIVER DISEASEThe Nonalcoholic Steatohepatitis (NASH) Clinical Research Network islaunching its first two clinical trials for the study of NASH, a liverdisease that resembles alcoholic liver disease but occurs in patients whodrink little or no alcohol. NASH occurs most often in adults over the age of40 who are overweight or have diabetes, insulin resistance (pre-diabetes),or hyperlipidemia (excess concentrations of fatty materials in the blood).NASH can also occur in children, the elderly, normal-weight, andnon-diabetic persons. The NASH Clinical Research Network and the clinicaltrial are funded by the National Institute of Diabetes and Digestive andKidney Diseases (NIDDK), one of the National Institutes of Health (NIH).NASH accounts for about 10 percent of newly diagnosed cases of chronic liverdisease, and ranks as one of the leading causes of cirrhosis in the UnitedStates, following hepatitis C and alcoholic liver disease. Characteristicsof the disease include abnormal liver enzyme levels, liver cell injury,inflammation and fibrosis in the liver, and excess amounts of fat stored inthe liver. Though most people with NASH feel healthy and show no outwardsigns of a liver disease, NASH is progressive and can lead to cirrhosis andend-stage liver disease, which may require liver transplantation. The onlyway to distinguish NASH from other forms of fatty liver disease is with aliver biopsy."NASH has become a serious public health problem, because the incidence ofNASH has risen with the increase of overweight and obesity in this country,"says Robuck, Ph.D., M.P.H., project scientist for the NASH ClinicalResearch Network and director of the Clinical Trials Program within theDivision of Digestive Diseases and Nutrition at the NIDDK.The NASH Clinical Research Network, consisting of eight clinical centers anda data coordinating center, was formed in September 2002 to conduct researchon the natural history, pathogenesis, and treatment of NASH. With theinformation collected from observational studies and clinical trials on bothadult and pediatric NASH patients, the Clinical Research Network will createa database of information to be used by researchers in the development oftherapies for NASH. The Network also plans to encourage collaborations amongclinical and basic researchers to generate information and develop ancillarystudies using the resources of the database.While there are currently no proven treatments for NASH, results from smallpilot trials suggest that certain diabetes drugs improve liver enzyme levelsand may slow or reverse the progression of NASH. Other pilot studiesindicate that patients with this liver disease show improvement by followinga regimen of balanced diet and exercise and also respond favorably totreatment with antioxidants such as vitamin E.The first two clinical trials for the NASH Clinical Research Network willfocus on the use of insulin-sensitizing agents and vitamin E for thetreatment of NASH in adults and in children. The first clinical trial, the"Pioglitazone versus Vitamin E versus Placebo for the Treatment ofNondiabetic Patients with Nonalcoholic Steatohepatitis" (PIVENS) trial iscurrently recruiting non-diabetic patients and will enroll 240 adults over 2years into one of three treatment groups. Men and women aged 18 years andolder will be assigned to either the vitamin E group, pioglitazone (aninsulin-sensitizing agent) group, or placebo group. Potential patientvolunteers will receive a standard oral glucose tolerance test after a12-hour fast to rule out the presence of diabetes. Volunteers will alsoundergo liver biopsies at the start and the end of the trial."We believe that even in the absence of diabetes, drugs that improve insulinresistance may improve NASH. The PIVENS trial will test the possibility thatboth pioglitazone and vitamin E are effective treatments for NASH," saysArun Sanyal, M.D., co-chair, NASH CRN and principal investigator for thecenter at Virginia Commonwealth University in Richmond.The second clinical trial, the "Treatment of Nonalcoholic Fatty LiverDisease (NAFLD) in Children" (TONIC) trial, will enroll 180 children withNAFLD to receive vitamin E, metformin (an insulin-sensitizing agent), orplacebo over 18 months. The TONIC trial will begin recruitment in June 2005."Having a clear understanding of the pathogenesis of NASH and its naturalhistory in both adults and children should translate into better treatmentsthat slow or prevent NASH from progressing, ultimately improving the qualityof life of patients with this liver disease," says Jay Hoofnagle, M.D.,director, NIDDK Liver Disease Research Branch.The eight clinical centers of the NASH Clinical Research Network recruitingpatients include: Case Western Reserve University in Cleveland; DukeUniversity Medical Center in Raleigh-Durham (adult site)/ s HopkinsUniversity in Baltimore (pediatric site); Indiana University inIndianapolis; St. Louis University in Missouri; University of California inSan Diego; University of California in San Francisco; University ofWashington in Seattle; and Virginia Commonwealth University in Richmond. Thes Hopkins University Bloomberg School of Public Health in Baltimoreprovides coordination of the research network data.The NASH Clinical Research Network and the PIVENS and TONIC clinical trialsare funded by the NIDDK and an industry partner, Takeda Pharmaceuticals.Additional funding is provided by the National Institute of Child Health andHuman Development, part of the NIH, an agency of the U.S. Department ofHealth and Human Services.Editors:Contact information for the centers is available at http://www.nashcrn.com.For general information about NASH, visithttp://digestive.niddk.nih.gov/diseases/pubs/nash/.