Over 50% of patients who require long-term (>4 weeks) total parenteral nutrition (TPN) develop hepatic steatosis (fatty liver). Left untreated, this condition may progress to cirrhosis and liver failure. Recent animal and human studies have shown that adding choline to the TPN mixture can reverse steatosis. Orphan Medical, Inc., a pharmaceutical company specializing in novel therapies for patients with uncommon diseases, proposes to develop and market choline chloride for this purpose. However, preventing hepatic steatosis can minimize adverse outcomes for chronic TPN patients. Therefore, the objective of the proposed study is to expand the medical usefulness of choline chloride by testing whether it can prevent as well as treat hepatic steatosis. In this open-label feasibility study, 10 patients starting long-term TPN for >80% of their nutritional needs will receive intravenous choline supplementation (2.0 g/day) daily for eight weeks. Serial CT scans will determine the relative degree of steatosis, and a GC/MS validated assay will be used to measure the plasma free choline levels. Positive results from the feasibility study would justify the large, randomized controlled trials necessary to achieve FDA approval and market the drug for prophylactic addition to TPN solutions in the nearly 200,000 patients currently at risk.Proposed commercial application:Adequate well-controlled clinical trials leading to an NDA would enable Orphan Medical to market choline for prevention and treatment of fatty liver to nearly 200,000 patients receiving long-term TPN in hospitals or at home. The company has acquired exclusive rights to develop and market the drug from its inventor, who has filed a US patent application and received orphan drug designation from the FDA. Once FDA approval is attained, this agreement assures market exclusivity for a minimum of 7 years.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
