Hepatic Histopathology in Urea Cycle Disorders

Recruiting

• Conditions: Urea Cycle Disorder; ASS Deficiency; Carbamyl Phosphate Synthetase Deficiency; Argininosuccinic Aciduria; Ornithine Transcarbamylase Deficiency; ASL Deficiency; Citrullinemia 1; ARGI Deficiency; Hyperargininemia; NAGS Deficiency

• Registration Number: NCT04908319
• Lead Sponsor: Baylor College of Medicine

Brief Summary

This is a multi-site, retrospective chart review as well as a prospective study to evaluate histopathologic findings in liver samples from individuals with any UCD diagnosis. This study will be conducted at all Urea Cycle Disorders Consortium (UCDC) sites: Baylor College of Medicine in Houston, TX 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.

Study Timeline

• Study First Submitted: 2021-05-26
• Study First Submitted QC: 2021-05-26
• Study First Posted: 2021-06-01
• Study Start: 2022-02-24
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-24
• Last Update Posted: 2024-05-28
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Diagnosis of primary urea cycle disorder based on clinical suspicion confirmed by enzyme activity, DNA testing or metabolite analysis.
• History of liver transplantation and/or liver biopsy OR
• Planned liver transplantation and/or liver biopsy

Exclusion Criteria

• Unavailability of histopathology report from the liver biopsy or explant, or unavailability of liver tissue or slides from the biopsy or explant OR
• Anticipated inability to obtain pathology report, liver disease, tissue blocks, or pathology slides after liver biopsy or transplantation
• Known history of a secondary cause for liver disease such as chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, or TPN-related cholestatic disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Steatosis	Day 1	Grade of steatosis from histopathology report from the liver biopsy or explant
Hepatic fibrosis	Day 1	Staging of fibrosis from histopathology report from the liver biopsy or explant
Hepatic glycogenosis	Day 1	Presence and type of glycogenosis from histopathology report from the liver biopsy or explant

Trial Locations

Locations (2)

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States