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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04612764
Other study ID # H-50295
Secondary ID
Status Recruiting
Phase
First received
Last updated
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
Health authority
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

Study Design


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)
See also
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