Liver Disease in Urea Cycle Disorders

Urea Cycle Disorder Clinical Trial

Official title:

Noninvasive Biomarkers of Hepatic Fibrosis in Urea Cycle Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04612764
• Other study ID #: H-50295
• Status: Recruiting
• Start date: November 4, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Baylor College of Medicine
• Contact: Saima Ali, MSN
• Phone: 832-822-4183
• Email: saima.ali[@]bcm.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• ARGI Deficiency
• Argininosuccinic Aciduria
• ASL Deficiency
• ASS Deficiency
• Citrullinemia
• Citrullinemia 1
• Hyperargininemia
• Ornithine Transcarbamylase Deficiency
• Urea Cycle Disorder
• Urea Cycle Disorders, Inborn

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Baylor College of Medicine	Houston	Texas
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (5)

Lead Sponsor	Collaborator
Baylor College of Medicine	Children's Hospital Colorado, Children's Hospital of Philadelphia, Children's National Research Institute, Seattle Children's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fibrotest	Fibrotest(TM)	One measurement made on the 1 day of the study visit (stage A)
Primary	Fibroscan (liver stiffness)	Liver stiffness (kPa) as assessed by Fibroscan®	One measurement made on the 1 day of the study visit (stage A)
Primary	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)
Primary	MRE	Liver stiffness (kPa) as measured by MRE	One measurement made on the 1 day of the study visit (stage B)
Secondary	Albumin	Albumin	One measurement made on the 1 day of the study visit (stage A)
Secondary	Liver Enzymes	Aspartate aminotransferase, Alanine aminotransaminase, and Gamma glutamyl transferase	One measurement made on the 1 day of the study visit (Stage A)
Secondary	Total Bilirubin	Total Bilirubin	One measurement made on the 1 day of the study visit (stage A)
Secondary	Prothrombin time	Prothrombin time	One measurement made on the 1 day of the study visit (stage A)
Secondary	INR	INR	One measurement made on the 1 day of the study visit (stage A)
Secondary	AST-to-Platelet Ratio (APRI)	AST-to-Platelet Ratio (APRI)	One measurement made on the 1 day of the study visit (stage A)
Secondary	GGT-to-Platelet Ratio (GPR)	GGT-to-Platelet Ratio (GPR)	One measurement made on the 1 day of the study visit (stage A)
Secondary	Fibrosis-4 (FIB-4) Index	Fibrosis-4 (FIB-4) Index	One measurement made on the 1 day of the study visit (stage A)
Secondary	MRE	Fat fraction (%) as measured by MRE	One measurement made on the 1 day of the study visit (stage B)