OBJECTIVES: I. Determine whether infants treated with tauroursodeoxycholic acid (TUDCA) have a lower peak direct bilirubin, ALT, AST, glutamyltranspeptidase levels and a reduced duration of cholestasis compared to the nontreatment arm. II. Determine the significance of lower birth weight and longer duration of total parenteral nutrition (TPN) on increasing risk of TPN associated cholestasis and increasing benefit from TUDCA therapy. III. Determine whether TUDCA therapy leads to significant reduction in the appearance of biliary tract sludge and/or stone formation in these infants. IV. Determine whether TUDCA therapy leads to reduced urinary excretion of potentially hepatotoxic bile acids as compared to the untreated arm matched for birth weight and duration of TPN.

Condition	Treatment or Intervention
Cholestasis	Drug: tauroursodeoxycholic acid

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by birth weight. Patients are randomized in pairs by birth weight to receive either a placebo in arm I or tauroursodeoxycholic acid (TUDCA) in arm II. TUDCA is administered by mouth, nasogastric tube, or gastrostomy tube twice daily. After 2 weeks of therapy, a bile sample is obtained via a duodenal tube. An ultrasound examination of the liver and biliary tract is performed after 2 weeks and every 3 weeks thereafter until discontinuation of therapy or until presence of biliary tract sludge is noted on 2 consecutive examinations.

Ages Eligible for Study:  up to  20 Days,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Hospitalized infants who are anticipated to require total parenteral nutrition for greater than 2 weeks and have: Major gastrointestinal anomalies (gastroschisis, ruptured omphalocele) OR Resection (necrotizing enterocolitis, volvulus)
• No evidence of biliary tract abnormalities
• No evidence of other forms of cholestatic liver disease

--Patient Characteristics--

• Renal: No life threatening renal disease
• Cardiovascular: No life threatening cardiovascular disease
• Other: No multiple congenital abnormalities

Minnesota
      Children's Hospitals and Clinics - Minneapolis, Minneapolis,  Minnesota,  55404,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States; Recruiting

Study chairs or principal investigators

James Heubi,  Study Chair,  Children's Hospital Medical Center - Cincinnati   

Study ID Numbers:  199/13299; CHMC-C-95-9-9; CHMC-C-CRC-473; CHMC-C-FDR001277
Record last reviewed:  August 1998
Record first received:  October 18, 1999
ClinicalTrials.gov Identifier:  NCT00004410
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-09