Liver Disease in Urea Cycle Disorders

NCT04612764 | Active Not Recruiting DMC

• 1 other identifier: H-50295
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 5

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.

Conditions

Urea Cycle Disorder; Ornithine Transcarbamylase Deficiency; Citrullinemia 1; ARGI Deficiency; ASL Deficiency; Argininosuccinic Aciduria; ASS Deficiency; Hyperargininemia

Keywords

Liver disease; Fibroscan; Magnetic resonance elastography; Fibrotest

Outcome Measures

Primary Outcomes (4)

• Fibrotest

  Fibrotest(TM)

  One measurement made on the 1 day of the study visit (stage A)

• Fibroscan (liver stiffness)

  Liver stiffness (kPa) as assessed by Fibroscan®

  One measurement made on the 1 day of the study visit (stage A)

• Fibroscan (CAP)

  Controlled Attenuation Parameter (CAPTM in dB/m) as assessed by Fibroscan®

  One measurement made on the 1 day of the study visit (stage A)

• MRE

  Liver stiffness (kPa) as measured by MRE

  One measurement made on the 1 day of the study visit (stage B)

Secondary Outcomes (9)

• Albumin

  One measurement made on the 1 day of the study visit (stage A)

• Liver Enzymes

  One measurement made on the 1 day of the study visit (Stage A)

• Total Bilirubin

  One measurement made on the 1 day of the study visit (stage A)

• Prothrombin time

  One measurement made on the 1 day of the study visit (stage A)

• INR

  One measurement made on the 1 day of the study visit (stage A)

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with urea cycle disorders

You may qualify if:

• Age \> 6 years and \< 65 years
• Weight ≥ 11 kg at time of screening
• A molecular or biochemical diagnosis of OTCD, ASS1D, ASLD, or ARG1D.

You may not qualify if:

• 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
• Participation in Stage A of this study
• Individuals with claustrophobia or other inability to complete
• Known diagnosis of hemochromatosis
• Presence of implants or devices incompatible with MRI
• Inability to breath-hold for 20 seconds for the elastography sequence
• Current pregnancy
• Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, short gut, small bowel syndrome, alcohol liver disease, TPN requirement, or TPN-related cholestatic disease
• Episode of documented acute hyperammonemia (ammonia ≥ 100 umol/L) in the 30 days prior to scheduled visit for Stage B

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Children's National Research Institute: collaborator
• Seattle Children's Hospital: collaborator
• Children's Hospital Colorado: collaborator
• Children's Hospital of Philadelphia: collaborator

Study Sites (5)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease; Citrullinemia; Hyperargininemia; Argininosuccinic Aciduria; Liver Diseases

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Genetic Diseases, X-Linked; Digestive System Diseases

Study Officials

• Lindsay Burrage, MD, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: November 3, 2020
• Study Start: November 4, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)