Liver Disease in Urea Cycle Disorders
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| ClinicalTrials.gov Identifier: NCT04612764 |
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Recruitment Status :
Recruiting
First Posted : November 3, 2020
Last Update Posted : May 6, 2023
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| Condition or disease |
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| Urea Cycle Disorder Ornithine Transcarbamylase Deficiency Citrullinemia 1 ARGI Deficiency ASL Deficiency Argininosuccinic Aciduria ASS Deficiency Hyperargininemia |
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
| Study Type : | Observational |
| Estimated Enrollment : | 62 participants |
| Observational Model: | Other |
| Time Perspective: | Cross-Sectional |
| Official Title: | Noninvasive Biomarkers of Hepatic Fibrosis in Urea Cycle Disorders |
| Actual Study Start Date : | November 4, 2021 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2023 |
- Fibrotest [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Fibrotest(TM)
- Fibroscan (liver stiffness) [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Liver stiffness (kPa) as assessed by Fibroscan®
- Fibroscan (CAP) [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Controlled Attenuation Parameter (CAPTM in dB/m) as assessed by Fibroscan®
- MRE [ Time Frame: One measurement made on the 1 day of the study visit (stage B) ]Liver stiffness (kPa) as measured by MRE
- Albumin [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Albumin
- Liver Enzymes [ Time Frame: One measurement made on the 1 day of the study visit (Stage A) ]Aspartate aminotransferase, Alanine aminotransaminase, and Gamma glutamyl transferase
- Total Bilirubin [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Total Bilirubin
- Prothrombin time [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Prothrombin time
- INR [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]INR
- AST-to-Platelet Ratio (APRI) [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]AST-to-Platelet Ratio (APRI)
- GGT-to-Platelet Ratio (GPR) [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]GGT-to-Platelet Ratio (GPR)
- Fibrosis-4 (FIB-4) Index [ Time Frame: One measurement made on the 1 day of the study visit (stage A) ]Fibrosis-4 (FIB-4) Index
- MRE [ Time Frame: One measurement made on the 1 day of the study visit (stage B) ]Fat fraction (%) as measured by MRE
Biospecimen Retention: Samples Without DNA
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| Ages Eligible for Study: | 6 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04612764
| Contact: Saima Ali, MSN | 832-822-4183 | saima.ali@bcm.edu |
| United States, Colorado | |
| Children's Hospital Colorado | Not yet recruiting |
| Aurora, Colorado, United States, 80045 | |
| Contact: Brittany Murphy 720-777-8591 Brittany.Murphy@childrenscolorado.org | |
| Principal Investigator: Shawn McCandless, MD | |
| United States, District of Columbia | |
| Children's National Medical Center | Recruiting |
| Washington, District of Columbia, United States, 20010 | |
| Contact: Kara Simpson, MS, CGC 202-476-6216 ksimpson@childrensnational.org | |
| Principal Investigator: Nicholas A Mew, MD | |
| United States, Pennsylvania | |
| The Children's Hospital of Philadelphia | Not yet recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact: Bianca Ferreira, MPH 267-426-1368 ferreirab@email.chop.edu | |
| Principal Investigator: Can Ficicioglu, MD, PhD | |
| United States, Texas | |
| Baylor College of Medicine | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Saima Ali 832-822-4183 saima.ali@bcm.edu | |
| Principal Investigator: Lindsay C Burrage, MD, PhD | |
| United States, Washington | |
| Seattle Children's Hospital | Not yet recruiting |
| Seattle, Washington, United States, 98105 | |
| Contact: Linnea Brody, CRA 206-987-3012 Linnea.brody@seattlechildrens.org | |
| Principal Investigator: Christina Lam, MD | |
| Principal Investigator: | Lindsay Burrage, MD, PhD | Baylor College of Medicine |
| Responsible Party: | Lindsay Burrage, Principal Investigator, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT04612764 |
| Other Study ID Numbers: |
H-50295 |
| First Posted: | November 3, 2020 Key Record Dates |
| Last Update Posted: | May 6, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Liver disease Fibroscan Magnetic resonance elastography Fibrotest |
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Urea Cycle Disorders, Inborn Ornithine Carbamoyltransferase Deficiency Disease Citrullinemia Argininosuccinic Aciduria Hyperargininemia 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 Metabolic Diseases Genetic Diseases, X-Linked |