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

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 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:

Genetics Home Reference related topics: CASK-related intellectual disability D-bifunctional protein deficiency MECP2 duplication syndrome PPM-X syndrome Refsum disease Renpenning syndrome SYNGAP1-related intellectual disability X-linked adrenoleukodystrophy Zellweger spectrum disorder alpha-methylacyl-CoA racemase deficiency familial glucocorticoid deficiency leukoencephalopathy with vanishing white matter megalencephalic leukoencephalopathy with subcortical cysts peroxisomal acyl-CoA oxidase deficiency succinic semialdehyde dehydrogenase deficiency

Drug Information available for: Cholic acid

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

U.S. FDA Resources

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:

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


Ages Eligible for Study:	Child, Adult, Senior
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

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: 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
Study First Received:	December 6, 2000
Last Updated:	April 15, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Adrenoleukodystrophy Cholestasis Peroxisomal Disorders Refsum Disease, Infantile Refsum Disease Zellweger Syndrome 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 Bile Duct Diseases Biliary Tract Diseases Digestive System Diseases Hereditary Sensory and Motor Neuropathy

Adrenoleukodystrophy
Cholestasis
Peroxisomal Disorders
Refsum Disease, Infantile
Refsum Disease
Zellweger Syndrome
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
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Hereditary Sensory and Motor Neuropathy

ClinicalTrials.gov processed this record on September 29, 2016