Clinical trial NCT03721367: Chronic Liver Disease in Urea Cycle Disorders
Official title: Prospective Cross-Sectional Non-invasive Assessment of Chronic Liver Disease in Urea Cycle Disorders
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urea Cycle Disorder
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Seattle Children's Hospital
name: University of California, San Francisco
First posted: 2018-10-26
Enrollment: 28
Sex: ALL
Minimum age (years): 5
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with urea cycle disorders

Brief summary: This is a pilot, cross-sectional study to assess liver stiffness and markers of hepatic injury, function, and fibrosis in patients with urea cycle disorders. This study will be conducted at 3 UCDC sites: Baylor College of Medicine in Houston, Texas, University of California San Francisco (UCSF), San Francisco, California and Seattle Children's Hospital, Seattle,Washington

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 purpose of this study is: 1) To determine whether liver stiffness is higher in individuals with ASS1D, ASLD, and ARG1D as compared to females with OTCD, and to assess liver stiffness in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD), 2) To test whether markers of hepatocellular injury and function and novel serum biomarker panels for hepatic fibrosis provide evidence of chronic liver disease in individuals with ASS1D, ASLD, and ARG1D as compared to OTCD and to assess these sample markers of hepatocellular injury and function and novel serum biomarker panels for hepatic fibrosis in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD).

Eligibility criteria: Inclusion Criteria:

1. Age \> 5 years and \< 60 years
2. Weight ≥ 11 kg
3. Males or females with a diagnosis of OTCD based on molecular or enzymatic testing. Males or females with a diagnosis of CPS1D, citrin deficiency, NAGSD, ASS1D, ASLD or ARG1D based on biochemical OR molecular, OR enzymatic testing

Exclusion Criteria:

1. History of hyperammonemia (blood ammonia greater than 100 micromoles/L) documented in the medical record or reported by the patient in the 30 days preceding enrollment visit
2. History of Liver transplantation
3. Current pregnancy
4. Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, or alcohol liver disease

Primary outcomes:
measure: Liver Stiffness as Measured by Shear Wave Elastography
timeFrame: One measurement made on the day of study visit
measure: Grey Scale Ultrasound Findings
timeFrame: Baseline, once
Secondary outcomes:
measure: Fibrotest
timeFrame: Baseline, once
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References:
citation: Nagamani SCS, Ali S, Izem R, Schady D, Masand P, Shneider BL, Leung DH, Burrage LC. Biomarkers for liver disease in urea cycle disorders. Mol Genet Metab. 2021 Jun;133(2):148-156. doi: 10.1016/j.ymgme.2021.04.001. Epub 2021 Apr 8.
citation: Burrage LC, Madan S, Li X, Ali S, Mohammad M, Stroup BM, Jiang MM, Cela R, Bertin T, Jin Z, Dai J, Guffey D, Finegold M; Members of the Urea Cycle Disorders Consortium (UCDC); Nagamani S, Minard CG, Marini J, Masand P, Schady D, Shneider BL, Leung DH, Bali D, Lee B. Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency. JCI Insight. 2020 Feb 27;5(4):e132342. doi: 10.1172/jci.insight.132342.