Longitudinal Study of Mitochondrial Hepatopathies
- Conditions
- Respiratory Chain Deficiencies, MitochondrialAcute Liver FailureDisorder of Fatty Acid OxidationMitochondrial DiseasesEnd Stage Liver Disease
- Registration Number
- NCT01148550
- Lead Sponsor
- Arbor Research Collaborative for Health
- Brief Summary
The specific aims of this study are (1) to determine the clinical phenotypes and natural history of hepatic RC and FAO disorders, (2) to determine the correlation between genotype and phenotype, (3) to determine if circulating biomarkers reflect diagnosis and predict liver disease progression and survival with the native liver, (4) to determine the clinical outcome of these disorders following liver transplantation, and (5) to develop a repository of serum, plasma, urine, tissue and DNA specimens that will be used in ancillary studies. To accomplish these aims, the ChiLDREN investigators at clinical sites (currently 15 sites) will prospectively collect defined data and specimens in a uniform fashion at fixed intervals in a relatively large number of subjects. Clinical information and DNA samples to be collected from subjects and their parents will enhance the potential for meaningful research in these disorders. A biobank of subject specimens and DNA samples will be established for use in ancillary studies to be performed in addition to this study.
- Detailed Description
This study will be conducted as part of the NIH-supported Childhood Liver Disease Research and Education Network (ChiLDREN). ChiLDREN is investigating rare cholestatic liver diseases of childhood: alpha-1 antitrypsin deficiency (A1AT), Alagille's Syndrome (AGS), progressive familial intrahepatic cholestasis (PFIC), bile acid synthesis defects and mitochondrial hepatopathies (all previously studied by the Cholestatic Liver Disease Consortium \[CLiC\]); biliary atresia (previously studied by the Biliary Atresia Research Consortium \[BARC\]); neonatal hepatitis; and cystic fibrosis liver disease, which is studied by a new branch of ChiLDREN known as the Cystic Fibrosis Liver Disease (CFLD) Network.
In this protocol, mitochondrial hepatopathies in children and young adults will be investigated. The focus will be on respiratory chain defects (RC) and defects of fatty acid oxidation (FAO). There is little known about the full spectrum of severity and long-term natural history of mitochondrial hepatopathies. Moreover, these disorders have not been subject to prospective, rigorous clinicopathological scrutiny.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 67
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Death Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Death
Liver transplantation Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Liver transplantation
Involvement of other organ systems known to be associated with mitochondrial diseases Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Involvement of other organ systems known to be associated with mitochondrial diseases
Listing for liver transplant Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Listing for liver transplant
- Secondary Outcome Measures
Name Time Method Complications of portal hypertension Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Complications of portal hypertension
Growth failure Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Growth failure (defined as weight or length Z-score for age \< -2)
Health related Quality of Life Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Health related Quality of Life
Neurodevelopmental outcome Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Neurodevelopmental outcome
Worsening liver function Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable Worsening liver function (defined as PELD \>10)
Trial Locations
- Locations (16)
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of California at San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's Healthcare of Atlanta - Emory University
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital
🇺🇸Chicago, Illinois, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Johns Hopkins School of Medicine
🇺🇸Baltimore, Maryland, United States
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Texas Children's Hospital (Baylor College of Medicine)
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada