Study of Tauroursodeoxycholic Acid for Hepatobiliary Disease in Cystic Fibrosis
Study of Tauroursodeoxycholic Acid for Hepatobiliary Disease in Cystic Fibrosis
OBJECTIVES: I. Determine the optimum dose of tauroursodeoxycholic acid (TUDCA) required to
 achieve maximal bioavailability for patients with cystic fibrosis-associated liver disease.

 II. Compare optimized doses of TUDCA with ursodiol (ursodeoxycholic acid; UDCA) for effects
 on biliary bile acid composition and metabolism, serum biochemistries, fat absorption, and
 fat-soluble vitamin status in these patients.
PROTOCOL OUTLINE: Objective I: This part of the study is a dose-response study to determine
 the optimal dose of tauroursodeoxycholic acid (TUDCA). Twenty-four patients are randomized to
 receive one of three different doses of TUDCA for 3 months.

 Objective II: This part of the study is a double-blind crossover study to compare optimized
 doses of TUDCA with optimized doses of ursodiol in 15 patients stratified according to age
 (less than 10 vs 10-20 vs more than 20 years). Patients are randomized to receive either
 TUDCA or ursodiol orally for an initial 3 month period, followed by a 3 month washout period
 in which no drug is administered. Patients then receive the alternate drug for 3 months.

 Completion date provided represents the completion date of the grant per OOPD records
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 -  Cystic fibrosis-associated liver disease, defined by at least one of the following
 criteria: (1) Documented increase in serum concentrations of any of the liver enzymes
 (at least once in the preceding year) ALT at least twice normal AST at least 1.5 times
 normal Alkaline phosphatase at least 1.5 times normal GGT at least 1.5 times normal
 (2) Persistent hepatomegaly of more than 6 months duration defined by percussed liver
 span greater than 1 SEM for age (3) Splenomegaly, defined as a palpable spleen greater
 than 2.0 cm below the left costal margin (4) Abnormalities of ultrasound scan
 (increased size, dishomogeneous echogenicity, nodular liver, irregular margins,
 splenomegaly) within 6 months prior to study entry

 -  Patients enrolled in the first part of the study (objective I) are eligible to
 participate in the second part (objective II)

 --Prior/Concurrent Therapy--

 -  At least 3 months since prior ursodiol

 -  At least 3 months since treatment with drug with choleretic properties or effects that
 influence bile acid metabolism

 --Patient Characteristics--

 -  Hepatic: No decompensated cirrhosis No hepatic neoplasm or cholelithiasis

 -  Pulmonary: No significantly impaired pulmonary function with FEV1 less than 50%

 -  Other: At least 15 kg body weight No severely compromised clinical or nutritional
 state