ARGI Deficiency, Argininosuccinic Aciduria, ASL Deficiency, ASS Deficiency, Citrullinemia 1, Hyperargininemia, Ornithine Transcarbamylase Deficiency, Urea Cycle Disorder
Conditions
Keywords
Liver disease, Fibroscan, Magnetic resonance elastography, Fibrotest
Brief summary
This is a multi-center, cross-sectional study to assess risk for liver fibrosis and hepatic injury in individuals with urea cycle disorders (UCDs) using serum biomarkers, Fibroscan, and MRE. This study will be conducted at 5 sites of the Urea Cycle Disorders Consortium: Baylor College of Medicine in Houston, TX, Seattle Children's Hospital in Seattle, WA, Children's Hospital Colorado in Aurora, CO, Children's Hospital of Philadelphia in Philadelphia, PA, and Children's National Medical Center in Washington D.C.
Detailed description
Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. With early diagnosis and improved treatments, the survival of individuals with UCDs has improved, and this improved survival has led to unmasking of some long-term complications such as hepatic dysfunction and progressive fibrosis in a subset of patients. Hepatic complications in UCDs are quite variable and dependent upon the specific metabolic defect. Currently, there are no guidelines for monitoring hepatic complications or extent of liver disease in UCDs. The gold standard for staging of fibrosis or confirming cirrhosis has traditionally been liver biopsy, an invasive procedure with inherent risks, particularly in the setting of a UCD and compromised coagulation. Recently, non-invasive serum and imaging-based biomarkers have been introduced to assess hepatic fibrosis in adults and children who are at increased risk. Utilization of these technique in individuals with UCDs could be invaluable in both the research and clinical arenas. The purpose of this study is: 1\) To assess risk for increased fibrosis using serum biomarkers and/or VCTE in distal disorders (ASS1D, ASLD and ARG1D) as compared to OTCD 2 ) To assess risk for hepatic fibrosis (liver stiffness as measured by MRE) in individuals with UCDs who have abnormal serum biomarkers and/or VCTE as those who have normal values
Interventions
None listed
Sponsors
Baylor College of Medicine
Children's National Research Institute
Seattle Children's Hospital
Children's Hospital Colorado
Children's Hospital of Philadelphia
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
6 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Stage A Inclusion Criteria: * Age \> 6 years and \< 65 years * Weight ≥ 11 kg at time of screening * A molecular or biochemical diagnosis of OTCD, ASS1D, ASLD, or ARG1D.
Exclusion criteria
* Prior liver transplantation * Episode of acute hyperammonemia (≥100 umol/L) in the 30 days prior to enrollment * Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, TPN requirement, or TPN-related cholestatic disease * Adults with BMI ≥ 45 kg/m2 * Current pregnancy * Open wound near expected Fibroscan® probe application site * Use of implantable active medical device such as cardiac pacemaker or implantable cardioverter-defibrillator Stage B Inclusion Criteria • Participation in Stage A of this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibrotest | One measurement made on the 1 day of the study visit (stage A) | Fibrotest(TM) |
| Fibroscan (liver stiffness) | One measurement made on the 1 day of the study visit (stage A) | Liver stiffness (kPa) as assessed by Fibroscan® |
| Fibroscan (CAP) | One measurement made on the 1 day of the study visit (stage A) | Controlled Attenuation Parameter (CAPTM in dB/m) as assessed by Fibroscan® |
| MRE | One measurement made on the 1 day of the study visit (stage B) | Liver stiffness (kPa) as measured by MRE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Albumin | One measurement made on the 1 day of the study visit (stage A) | Albumin |
| Liver Enzymes | One measurement made on the 1 day of the study visit (Stage A) | Aspartate aminotransferase, Alanine aminotransaminase, and Gamma glutamyl transferase |
| Total Bilirubin | One measurement made on the 1 day of the study visit (stage A) | Total Bilirubin |
| Prothrombin time | One measurement made on the 1 day of the study visit (stage A) | Prothrombin time |
| INR | One measurement made on the 1 day of the study visit (stage A) | INR |
| AST-to-Platelet Ratio (APRI) | One measurement made on the 1 day of the study visit (stage A) | AST-to-Platelet Ratio (APRI) |
| GGT-to-Platelet Ratio (GPR) | One measurement made on the 1 day of the study visit (stage A) | GGT-to-Platelet Ratio (GPR) |
| Fibrosis-4 (FIB-4) Index | One measurement made on the 1 day of the study visit (stage A) | Fibrosis-4 (FIB-4) Index |
| MRE | One measurement made on the 1 day of the study visit (stage B) | Fat fraction (%) as measured by MRE |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLindsay Burrage, MD, PhD
Baylor College of Medicine
Outcome results
None listed