efficacy of to be marketed (tbm) cholic acid capsules used to treat children with inborn errors of bile acid synthesis

Conditions: Inborn Errors of Bile Acid Synthesis

Summary: this is a study in a small population of children who have inborn errors of bile acid synthesis who are currently taking established doses of the currently used cholic acid capsules prepared at the cincinnati children's hospital pharmacy. the study is designed to compare the efficacy of these currently used capsules with the efficacy of the same treatment provided in a cholic acid capsule that is made by a company that will be marketed after fda approval. at baseline, patients receive established doses of cholic acid capsules prepared at the cincinnati children's hospital medical center pharmacy. during the study, patients receive the same treatment provided in the to-be-marketed (tbm) cholic acid capsule. hence, patients serve as their own controls, with baseline values presenting the reference value (cchmc cholic acid capsule) and values after 30 days treatment presenting the value for the investigational treatment (tbm cholic acid capsule).

bile acids are end products of cholesterol metabolism. individuals with inborn errors of bile acid synthesis lack the enzymes needed to synthesize the primary bile acids cholic acid and chenodeoxycholic acid (cdca). these conditions are serious and account for approximately 1% of cases presenting as idiopathic cholestatic liver disease. the liver disease associated with these inborn errors in bile acid synthesis is progressive and, if untreated, may lead to death from cirrhosis and liver failure. monotherapy with cholic acid is considered the most appropriate therapeutic strategy to treat inborn errors in bile acid synthesis because it provides a stimulus for bile flow and inhibits endogenous production and accumulation of potentially hepatotoxic and cholestatic bile acid precursors, while additionally facilitating the absorption of fats and fat-soluble vitamins. at therapeutic doses, adverse effects are not generally observed and as such, cholic acid has become the treatment of choice at the cincinnati children's hospital since 1994. this study will bridge data on the effectiveness of a standardized manufactured preparation to data obtained from patients originally treated with the currently used cholic acid capsules formulated in the cchmc pharmacy before being switched to the manufactured preparation.

Eligibility criteria:
inclusion criteria: * must have stable transaminase levels within 2 times the upper limits of the normal range. * must have a diagnosis of an inborn error of bile acid synthesis. * must have signed the written informed consent/assent document before study start. * must be currently receiving currently used cholic acid therapy under ind 45,470. * must be willing and able to comply with all study assessments and procedures. * must be able to make two visits (visit 1 and visit 2) to the study site. exclusion criteria: * is not currently receiving cholic acid therapy for inborn errors of bile acid synthesis under ind 45,470. * is unable or unwilling to comply with study requirements.

Keywords: inborn errors bile acid pediatrics liver disease