Clinical trial NCT01589523: GlycoCholic Acid Treatment for Patients With Inborn Errors in Bile Acid Synthesis
Official title: Conjugated Cholic Acid for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-Chain Conjugation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bile Acid Synthesis Defect
Inborn Error of Bile Acid Metabolism
Inborn Error of Bile Acid Conjugation
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2012-05-02
Enrollment: 5
Sex: ALL
Minimum age (years): 1
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine the way (mechanisms) by which your defect in bile acid handling (metabolism) causes your liver disease or abnormality in absorption of vitamins and the effect of an investigational bile acid therapy (glycocholic acid) on your vitamin absorption and your liver disease. An investigational therapy is one that not approved by the United States Food and Drug Administration (FDA) and is being provided to you under an Investigational New Drug application from the FDA.

Detailed description: Inborn errors of bile acid metabolism have been established as a well recognized cause of neonatal cholestasis and fat-soluble vitamin malabsorption. Although there is extensive experience with metabolic defects in the biosynthetic pathway, few patients have identified with defects in conjugation with taurine or glycine that allows bile acids to become effective detergents. This protocol is designed to study the effect of defects of conjugation of bile acids on growth and fat-soluble vitamin malabsorption. Study subjects will have liver function studies performed, serum and urinary bile acid measurements, vitamin levels, growth measurements, bile acid pool size measurements made by stable isotope dilution mass-spectrometry, and measurements of absorption of two fat-soluble vitamins, tocopherol and vitamin D. Subjects will be treated orally with conjugates of cholic acid with follow-up laboratories performed as an outpatient and then subjects will have all of the initial studies repeated during an inpatient stay 3-12 months after starting treatment. Subjects with previous liver biopsies indicating the presence of significant liver disease will have a repeat liver biopsy after 3-12 months treatment to assess the histologic response to treatment.

Eligibility criteria: Inclusion Criteria:

1. Confirmation of a diagnosis of an inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
2. Any age
3. Participant must be willing and able to comply with study assessments and procedures.
4. The participant and/or parent/legal guardian must have signed the written informed consent document prior to study start.

Exclusion Criteria

1. No confirmed diagnosis of inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.

Primary outcomes:
measure: Conjugated Cholic Acid (GCA) for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-chain Conjugation.
timeFrame: Up to 10 years
measure: Evaluation of Levels of Atypical Bile Acid Metabolites After GCA Treatment Compared
timeFrame: Average of 6 months, average 12 months, and average of after year 1 to 10 years
Secondary outcomes:
measure: Changes in Liver Function Tests of ALT From Baseline to Post-treatment
timeFrame: Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)
measure: Change in Liver Function Test: AST From Baseline to Post-treatment
timeFrame: Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)
measure: Change in Vitamin D, 25-OH Measure From Baseline to Post-treatment
timeFrame: Pre-treatment and post treatment (average of available timepoints after year 1 through year 10)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Kenneth D. Setchell, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: James E. Heubi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Setchell KD, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O'Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology. 2013 May;144(5):945-955.e6; quiz e14-5. doi: 10.1053/j.gastro.2013.02.004. Epub 2013 Feb 13.
citation: Heubi JE, Setchell KD, Jha P, Buckley D, Zhang W, Rosenthal P, Potter C, Horslen S, Suskind D. Treatment of bile acid amidation defects with glycocholic acid. Hepatology. 2015 Jan;61(1):268-74. doi: 10.1002/hep.27401. Epub 2014 Dec 23.