GlycoCholic Acid Treatment for Patients With Inborn Errors in Bile Acid Synthesis

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01589523
First received: April 3, 2012
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Bile Acid Synthesis Defect
Inborn Error of Bile Acid Metabolism
Inborn Error of Bile Acid Conjugation
Drug: Glycocholic Acid
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Conjugated Cholic Acid for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-Chain Conjugation

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Evaluation of Atypical Bile Acid Metabolites [ Time Frame: Comparison between baseline and follow-up visits at 3, 6 and 12 months for the first year and then an average of yearly visits for at least 10 years. ] [ Designated as safety issue: No ]
    Determination of changes in synthesis of atypical bile acids in urine by mass spectrometry (FAB MS)


Secondary Outcome Measures:
  • Liver Function tests [ Time Frame: Comparison between baseline and follow-up visits at 3, 6 and 12 months for the first year and then an average of yearly visits for at least 10 years. ] [ Designated as safety issue: No ]
    Liver function tests to include: total and direct bilirubin, ALT, AST, GGT, alkaline phosphatase, cholesterol, albumin, prothrombin time

  • Fat Soluble Vitamin Malabsorption [ Time Frame: Comparison between baseline and follow-up visits at 3, 6 and 12 months for the first year and then an average of yearly visits for at least 10 years. ] [ Designated as safety issue: No ]
    Measure Vitamin E and 25OH Vitamin D to assess vitamin absorption status

  • Growth parameters [ Time Frame: Standard of care (an average of every 6-12 months). ] [ Designated as safety issue: No ]
    Determine growth rate with height, weight and head circumference

  • Safety Assessments [ Time Frame: 3 months after initiation of therapy and then an average of yearly or more frequently as standard of care for at least 10 years. ] [ Designated as safety issue: Yes ]
    Incidence and severity of adverse events


Estimated Enrollment: 20
Study Start Date: February 2006
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GlycoCholic Acid, Study Drug
A Phase III, open label, single arm, non-randomized, non-comparative, treatment study of Glycocholic Acid in the treatment of defects of bile acid metabolism.
Drug: Glycocholic Acid
10-15mg/kg body weight/day taken orally. Supplied as either liquid or 50mg capsules.
Other Names:
  • Glycocholic Acid
  • Conjugated Cholic Acid

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

Ages Eligible for Study:   up to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589523

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Kenneth D.R. Setchell, Ph.D. Children's Hospital Medical Center, Cincinnati
Principal Investigator: James E. Heubi, M.D. Children's Hospital Medical Center, Cincinnati
  More Information

Publications:
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01589523     History of Changes
Other Study ID Numbers: 2009-0780
Study First Received: April 3, 2012
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glycocholic Acid
Cholic Acids
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014