This program supports patient-oriented clinical research in liver diseases to evaluate one or more experimental intervention(s) in comparison with a standard treatment and/or placebo control among comparable groups of patients. Experimental interventions may include pharmacologic, nonpharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Areas of program emphasis in liver disease include non-alcoholic steatohepatitis (NASH); chronic hepatitis C; primary biliary cirrhosis; primary sclerosing cholangitis; prevention, management, and treatment of portal hypertension; and recurrent liver disease after transplantation. Either pilot studies or phase III trials may be appropriate. A phase III clinical trial usually involves several hundred or more comparable human subjects, the aim of the trial being to provide evidence for support of, or a change in, health policy or standard of care.
Clinical trials and prospective clinical studies in liver disease that are currently funded by the Division of Digestive Diseases and Nutrition include:
- HALT-C, a study of long-term therapy with peginterferon in patients with chronic hepatitis C and advanced fibrosis who have failed to respond to standard therapy;
- Virahep-C, a study of peginterferon and ribavirin combination therapy in African American and Caucasian patients focusing upon the frequency and biological basis for non-response to antiviral treatment;
- Peds-C, a study of peginterferon with or without ribavirin as therapy of hepatitis C in children and adolescents;
- Nonalcoholic "" Steatohepatitis (NASH) Clinical Research Network, a prospective database and "" natural history study that includes a prospective randomized controlled trial in adults of a thiazolidinedione (pioglitazone) versus vitamin E or placebo and a similar trial in children of metformin versus vitamin E or placebo as therapy for NASH;
- Biliary Atresia Clinical Research Consortium (BARC), which is a prospective database on children with biliary atresia and includes a prospective randomized controlled trial of corticosteroids vs. placebo for improvement of bile flow after portoenterostomy surgery. BARC has recently been expanded to include a prospective study of children with rare neonatal cholestatic liver diseases (Cholestatic .Liver Disease Consortium: CLIC) including Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familial intrahepatic cholestasis (PFIC), mitochondrial hepatopathy and inborn errors of bile acid metabolism;
- Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL), which is a prospective and retrospective database on both donors and recipients of a living donor liver transplant which focuses on issues of donor informed consent and the quality of life, disease recurrence, and survival of recipients after liver donor liver transplantation; A2ALL is also initiating a randomized controlled trial of peginterferon and ribavirin therapy for patients with chronic hepatitis C (genotype 1) awaiting living donor liver transplantation;
- Acute Liver Failure Study Group, a prospective database and natural history study of acute liver failure and a randomized controlled trial of N-acetyl cysteamine for patients with acute liver failure that is not due to acetaminophen;
- Drug-Induced Liver Injury Network (DILIN), which is a prospective and retrospective database on cases of drug-induced liver injury.
- High dose Ursodiol Therapy for Primary Sclerosing Cholangitis, which is a prospective randomized controlled trial of ursodiol versus placebo being conducted by five clinical centers.
Clinical trials may be funded by one of several mechanisms: a research project grant, a cooperative agreement, a planning grant, or a contract. Please see the current program announcement for small grants for clinical trials.
For more information, contact Dr. Patricia R. Robuck, Program Director for Clinical Trials in Liver Diseases.
