Liver Disease in Urea Cycle Disorders

NCT ID: NCT04612764

Last Updated: 2025-04-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

62 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-11-04

Study Completion Date

2025-12-31

Brief Summary

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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

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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

Conditions

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

Study Design

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Observational Model Type

OTHER

Study Time Perspective

CROSS_SECTIONAL

Eligibility Criteria

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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.


• Participation in Stage A of this study

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


* 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
Minimum Eligible Age

6 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's National Research Institute

OTHER

Sponsor Role collaborator

Seattle Children's Hospital

OTHER

Sponsor Role collaborator

Children's Hospital Colorado

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Lindsay Burrage

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lindsay Burrage, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

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Children's Hospital Colorado

Aurora, Colorado, United States

Site Status NOT_YET_RECRUITING

Children's National Medical Center

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

Site Status RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Saima Ali, MSN

Role: CONTACT

832-822-4183

Facility Contacts

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Brittany Murphy

Role: primary

720-777-8591

Kara Simpson, MS, CGC

Role: primary

202-476-6216

Bianca Ferreira, MPH

Role: primary

267-426-1368

Saima Ali

Role: primary

832-822-4183

Linnea Brody, CRA

Role: primary

206-987-3012

Other Identifiers

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H-50295

Identifier Type: -

Identifier Source: org_study_id

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