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

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ClinicalTrials.gov Identifier: NCT00007020

Recruitment Status : Completed

First Posted : December 7, 2000

Last Update Posted : May 6, 2015

Sponsor:

Collaborator:

Children's Hospital Medical Center, Cincinnati

Information provided by (Responsible Party):

Retrophin, Inc.

Study Description

Brief Summary:

OBJECTIVES:

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 or disease	Intervention/treatment	Phase
Infantile Refsum's Disease Zellweger Syndrome Adrenoleukodystrophy Peroxisomal Disorders Cholestasis	Drug: Cholic Acids	Phase 3

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:

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

Time and Events Schedule:

Baseline:

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

Baseline and Ongoing:
Obtain body weight
Record adverse events
Obtain blood and urine samples for laboratory tests
Initiate study drug therapy & monitor study drug therapy and adjust dose as needed

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	79 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	January 1992
Actual Primary Completion Date :	December 2009
Actual Study Completion Date :	December 2009

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: D-bifunctional protein deficiency RNAse T2-deficient leukoencephalopathy Refsum disease X-linked adrenoleukodystrophy Zellweger spectrum disorder Alpha-methylacyl-CoA racemase deficiency Leukoencephalopathy with vanishing white matter Megalencephalic leukoencephalopathy with subcortical cysts Peroxisomal acyl-CoA oxidase deficiency

Drug Information available for: Cholic acid

Genetic and Rare Diseases Information Center resources: X-linked Adrenoleukodystrophy Adrenomyeloneuropathy Peroxisomal Biogenesis Disorders Refsum Disease Zellweger Syndrome Refsum Disease, Infantile Form Hypoadrenalism Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsy Roussy Levy Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Cholic Acid	Drug: Cholic Acids 10-15 mg/kg body weight/day taken orally. Other Names: Cholic Cholic Acid Cholic Acid Capsules

Outcome Measures

Primary Outcome Measures :

Determination of changes in synthesis of atypical bile acids in urine by mass spectrometry (FAB MS) [ Time Frame: 12 months ]

Secondary Outcome Measures :

Change in Liver Function Test (serum transaminases) [ Time Frame: Standard of Care ]
Change in Liver Histology (for patients in whom biopsy was performed) [ Time Frame: Standard of Care ]
Safety Assessments (Incidence and Severity of Adverse Events) [ Time Frame: Each visit as standard of care ]
Height and Weight [ Time Frame: Standard of Care ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

--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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00007020

Locations


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

Investigators


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.
ClinicalTrials.gov Identifier:	NCT00007020 History of Changes
Other Study ID Numbers:	CAC-91-10-10 CCHMC-91-10-10 ( Other Identifier: Cincinnati Children's Hospital Medical Center )
First Posted:	December 7, 2000 Key Record Dates
Last Update Posted:	May 6, 2015
Last Verified:	April 2015

Additional relevant MeSH terms:


Adrenoleukodystrophy Cholestasis Peroxisomal Disorders Zellweger Syndrome Refsum Disease, Infantile Refsum Disease Bile Duct Diseases Biliary Tract Diseases Digestive System Diseases Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Hereditary Central Nervous System Demyelinating Diseases	Leukoencephalopathies Demyelinating Diseases Mental Retardation, X-Linked Intellectual Disability Neurobehavioral Manifestations Neurologic Manifestations Genetic Diseases, X-Linked Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Metabolism, Inborn Errors Metabolic Diseases Adrenal Insufficiency Adrenal Gland Diseases Endocrine System Diseases Liver Diseases

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