Chronic Liver Disease in Urea Cycle Disorders

• ClinicalTrials.gov Identifier: NCT03721367
• Recruitment Status: Completed
• First Posted: October 26, 2018
• Last Update Posted: July 8, 2020
• Sponsor: Baylor College of Medicine
• Collaborators: Seattle Children's Hospital; University of California, San Francisco
• Information provided by (Responsible Party): Lindsay Burrage, Baylor College of Medicine

Study Description

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

Condition or disease	Intervention/treatment
Urea Cycle Disorder	Other: Diagnostic Ultrasound

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).

Study Design

• Study Type: Observational
• Actual Enrollment: 28 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: Prospective Cross-Sectional Non-invasive Assessment of Chronic Liver Disease in Urea Cycle Disorders
• Actual Study Start Date: November 29, 2017
• Actual Primary Completion Date: June 1, 2020
• Actual Study Completion Date: June 1, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Urea Cycle Disorders	Other: Diagnostic Ultrasound; All individuals will undergo a blood draw for measurement of biomarkers of liver disease and an ultrasound with shear-wave elastography.

Outcome Measures

Primary Outcome Measures :

1. Liver shear wave velocity in m/s as measured by shear wave elastography [ Time Frame: One measurement made on the day of study visit ]

Biospecimen Retention:   Samples Without DNA

Blood

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 60 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Individuals with urea cycle disorders

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

Contacts and Locations

Locations

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Sponsors and Collaborators

Baylor College of Medicine

Seattle Children's Hospital

University of California, San Francisco

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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). pii: 132342. doi: 10.1172/jci.insight.132342.

• Responsible Party: Lindsay Burrage, Assistant Professor, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT03721367
• Other Study ID Numbers: H-40988; UCDC 5118 ( Other Identifier: Urea Cycle Disorders Consortium )
• First Posted: October 26, 2018
• Last Update Posted: July 8, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Urea Cycle Disorders, Inborn; Digestive System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases