Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid - Full Text View

Sponsor:	Asklepion Pharmaceuticals, LLC
Collaborator:	Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):	Asklepion Pharmaceuticals, LLC
ClinicalTrials.gov Identifier:	NCT00007020

Purpose

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	Intervention	Phase
Infantile Refsum's Disease Zellweger Syndrome Adrenoleukodystrophy Peroxisomal Disorders Cholestasis	Drug: Cholic Acids	Phase III

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:

Genetics Home Reference related topics: beta-ketothiolase deficiency leukoencephalopathy with vanishing white matter MECP2 duplication syndrome megalencephalic leukoencephalopathy with subcortical cysts PPM-X syndrome Refsum disease succinic semialdehyde dehydrogenase deficiency X-linked adrenoleukodystrophy Zellweger spectrum Help Me Understand Genetics

MedlinePlus related topics: Liver Diseases

Drug Information available for: Cholic acid

U.S. FDA Resources

Further study details as provided by Asklepion Pharmaceuticals, LLC:

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:	83
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:

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

Eligibility

Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00007020

Locations

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039

Sponsors and Collaborators

Asklepion Pharmaceuticals, LLC

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

No publications provided

Responsible Party:	Asklepion Pharmaceuticals, LLC
ClinicalTrials.gov 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:	September 21, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Cholestasis
Refsum Disease
Zellweger Syndrome
Adrenoleukodystrophy
Refsum Disease, Infantile
Peroxisomal Disorders
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 Sensory and Motor Neuropathy

Nervous System Malformations
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Metabolic Diseases
Liver Diseases
Kidney Diseases
Urologic Diseases
Abnormalities, Multiple
Hereditary Central Nervous System Demyelinating Diseases

ClinicalTrials.gov processed this record on February 09, 2012