Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid

This study has been completed.
Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
Retrophin, Inc. Identifier:
First received: December 6, 2000
Last updated: April 15, 2015
Last verified: April 2015


I. To Evaluate the therapeutic efficacy of cholic acid during provision of compassionate treatment to patients with identified inborn errors of bile acid synthesis and metabolism

II. To assess the safety and tolerability of cholic acid

Condition Intervention Phase
Infantile Refsum's Disease
Zellweger Syndrome
Peroxisomal Disorders
Drug: Cholic Acids
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism." This Study Was Previously Registered by the NCRR and Identified as NCRR-M01RR08084-0009

Resource links provided by NLM:

Further study details as provided by Retrophin, Inc.:

Primary Outcome Measures:
  • Determination of changes in synthesis of atypical bile acids in urine by mass spectrometry (FAB MS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Liver Function Test (serum transaminases) [ Time Frame: Standard of Care ] [ Designated as safety issue: No ]
  • Change in Liver Histology (for patients in whom biopsy was performed) [ Time Frame: Standard of Care ] [ Designated as safety issue: No ]
  • Safety Assessments (Incidence and Severity of Adverse Events) [ Time Frame: Each visit as standard of care ] [ Designated as safety issue: Yes ]
  • Height and Weight [ Time Frame: Standard of Care ] [ Designated as safety issue: No ]

Enrollment: 79
Study Start Date: January 1992
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cholic Acid Drug: Cholic Acids
10-15 mg/kg body weight/day taken orally.
Other Names:
  • Cholic
  • Cholic Acid
  • Cholic Acid Capsules

Detailed Description:

Investigational Plan:

A Phase III, open label, single arm, nonrandomized, non-comparative, compassionate treatment study of cholic acid in the treatment of defects of bile acid metabolism.

The study was begun with a single study site at Cincinnati Children's Hospital Medical Center (CCHMC), but in 2005 was expanded so that compassionate treatment could be provided to additional patients who had been identified with inborn errors of bile metabolism through the center's screening/diagnostic program.

Patients who were screened were contacted and evaluated with respect to the inclusion/exclusion criteria. Signed informed consent by the patient and/or parents/legal guardian was obtained as soon as it is confirmed that the patient met inclusion/exclusion criteria and the parents/guardian would agree for the child to participate in the study.

The primary interventions for the study were:

  1. Administration of study drug.
  2. Collection of baseline physical exam, vital signs, blood and urine samples for laboratory tests.
  3. Collection of periodic physical exam, vital signs, blood and urine samples for laboratory tests during the period of administration of the study drug.
  4. Collection of any adverse event information.

Time and Events Schedule:


  1. Confirm eligibility
  2. Obtain written informed consent from patient and/or parents/legal guardian
  3. Collect demographic data and disease and medication history, including family history

    Baseline and Ongoing:

  4. Obtain body weight
  5. Record adverse events
  6. Obtain blood and urine samples for laboratory tests
  7. Initiate study drug therapy & monitor study drug therapy and adjust dose as needed

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


--Disease Characteristics--

Clinical or biochemical evidence of liver disease, unexplained fat-soluble vitamin malabsorption, or peroxisomal dysfunction that compromises bile acid biosynthesis

Inclusion criteria for enrollment were:

  • Infants < age 3 months
  • Children presenting for evaluation of cholestasis defined as a conjugated bilirubin > 2mg/dl or increased serum bile acids
  • Older subjects of any age with cholestatic liver disease if urine screens suggested that they had inborn errors of bile acid metabolism
  • Confirmation of a diagnosis of an inborn error of bile acid synthesis based upon urine analysis by FAB-MS to determine whether specific abnormalities in bile acid synthesis are indicated
  • The patient and/or parent/legal guardian must have signed the written informed consent document before study start.
  • The patient must be willing and able to comply with all study assessments and procedures.
  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 identifier: NCT00007020

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Sponsors and Collaborators
Retrophin, Inc.
Children's Hospital Medical Center, Cincinnati
Principal Investigator: James Heubi, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Kenneth Setchell, PhD Children's Hospital Medical Center, Cincinnati
  More Information

Responsible Party: Retrophin, Inc. Identifier: NCT00007020     History of Changes
Other Study ID Numbers: CAC-91-10-10  CCHMC-91-10-10 
Study First Received: December 6, 2000
Last Updated: April 15, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mental Retardation, X-Linked
Peroxisomal Disorders
Refsum Disease
Refsum Disease, Infantile
Zellweger Syndrome
Abnormalities, Multiple
Adrenal Gland Diseases
Adrenal Insufficiency
Bile Duct Diseases
Biliary Tract Diseases
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Congenital Abnormalities
Demyelinating Diseases
Digestive System Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hereditary Central Nervous System Demyelinating Diseases
Hereditary Sensory and Motor Neuropathy
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Kidney Diseases
Liver Diseases
Metabolic Diseases processed this record on May 30, 2016