Clinical trial NCT04612764: Liver Disease in Urea Cycle Disorders
Official title: Noninvasive Biomarkers of Hepatic Fibrosis in Urea Cycle Disorders
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Children's National Research Institute
name: Seattle Children's Hospital
name: Children's Hospital Colorado
name: Children's Hospital of Philadelphia
First posted: 2020-11-03
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_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 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: 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

Eligibility criteria: Stage A

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.

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

Stage B Inclusion Criteria

• Participation in Stage A of this study

Exclusion Criteria

* 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

Primary outcomes:
measure: Fibrotest
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: Fibroscan (liver stiffness)
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: Fibroscan (CAP)
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: MRE
timeFrame: One measurement made on the 1 day of the study visit (stage B)
Secondary outcomes:
measure: Albumin
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: Liver Enzymes
timeFrame: One measurement made on the 1 day of the study visit (Stage A)
measure: Total Bilirubin
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: Prothrombin time
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: INR
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: AST-to-Platelet Ratio (APRI)
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: GGT-to-Platelet Ratio (GPR)
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: Fibrosis-4 (FIB-4) Index
timeFrame: One measurement made on the 1 day of the study visit (stage A)
measure: MRE
timeFrame: One measurement made on the 1 day of the study visit (stage B)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Baylor College of Medicine
name: Lindsay Burrage, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: