Urea Cycle Disorder
Conditions
Brief summary
This is a pilot, cross-sectional study to assess liver stiffness and markers of hepatic injury, function, and fibrosis in patients with urea cycle disorders. This study will be conducted at 3 UCDC sites: Baylor College of Medicine in Houston, Texas, University of California San Francisco (UCSF), San Francisco, California and Seattle Children's Hospital, Seattle,Washington
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 purpose of this study is: 1) To determine whether liver stiffness is higher in individuals with ASS1D, ASLD, and ARG1D as compared to females with OTCD, and to assess liver stiffness in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD), 2) To test whether markers of hepatocellular injury and function and novel serum biomarker panels for hepatic fibrosis provide evidence of chronic liver disease in individuals with ASS1D, ASLD, and ARG1D as compared to OTCD and to assess these sample markers of hepatocellular injury and function and novel serum biomarker panels for hepatic fibrosis in other UCDs (citrin deficiency, NAGSD, CPS1D, and males with OTCD).
Interventions
All individuals will undergo a blood draw for measurement of biomarkers of liver disease and an ultrasound with shear-wave elastography.
Sponsors
Seattle Children's Hospital
University of California, San Francisco
Baylor College of Medicine
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
5 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age \> 5 years and \< 60 years 2. Weight ≥ 11 kg 3. Males or females with a diagnosis of OTCD based on molecular or enzymatic testing. Males or females with a diagnosis of CPS1D, citrin deficiency, NAGSD, ASS1D, ASLD or ARG1D based on biochemical OR molecular, OR enzymatic testing
Exclusion criteria
1. History of hyperammonemia (blood ammonia greater than 100 micromoles/L) documented in the medical record or reported by the patient in the 30 days preceding enrollment visit 2. History of Liver transplantation 3. Current pregnancy 4. Confirmed diagnosis of chronic viral hepatitis, autoimmune liver disease, or alcohol liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liver Stiffness as Measured by Shear Wave Elastography | One measurement made on the day of study visit | Shear wave elastography in m/s is a measure of liver stiffness, a surrogate measure for hepatic fibrosis. Normal liverstiffness is \< 1.35 m/s and abnormal liver stiffness is \>1.35 m/s |
| Grey Scale Ultrasound Findings | Baseline, once | Grey scale ultrasound findings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fibrotest | Baseline, once | Fibrotest is a blood test that is a surrogate measure for hepatic fibrosis. F0 is normal. \>F0 predicts at least minimal fibrosis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Urea Cycle Disorders Diagnostic Ultrasound: All individuals will undergo a blood draw for measurement of biomarkers of liver disease and an ultrasound with shear-wave elastography. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Urea Cycle Disorders |
|---|---|
| Age, Continuous | 15 years |
| BMI Healthy | 12 Participants |
| BMI Obese | 10 Participants |
| BMI Overweight | 5 Participants |
| BMI Underweight | 1 Participants |
| History of Hyperammonemia | 16 Participants |
| Race/Ethnicity, Customized African-American | 3 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 9 Participants |
| Race/Ethnicity, Customized Native American | 2 Participants |
| Race/Ethnicity, Customized White | 13 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 12 Participants |
| UCD diagnosis ARG1 Deficiency | 6 Participants |
| UCD diagnosis ASL Deficiency | 8 Participants |
| UCD diagnosis ASS1 Deficiency | 4 Participants |
| UCD diagnosis OTC Deficiency (Female) | 7 Participants |
| UCD diagnosis OTC Deficiency (Male) | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Grey Scale Ultrasound Findings
Grey scale ultrasound findings
Time frame: Baseline, once
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Urea Cycle Disorders | Grey Scale Ultrasound Findings | Normal hepatic parenchyma on grey scale ultrasound | 15 Participants |
| Urea Cycle Disorders | Grey Scale Ultrasound Findings | Abnormal hepatic parenchyma on grey scale ultrasound | 13 Participants |
Primary
Liver Stiffness as Measured by Shear Wave Elastography
Shear wave elastography in m/s is a measure of liver stiffness, a surrogate measure for hepatic fibrosis. Normal liverstiffness is \< 1.35 m/s and abnormal liver stiffness is \>1.35 m/s
Time frame: One measurement made on the day of study visit
Population: The data for this outcome was reliable for only 27 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Urea Cycle Disorders | Liver Stiffness as Measured by Shear Wave Elastography | Abnormal Liver Stiffness | 14 Participants |
| Urea Cycle Disorders | Liver Stiffness as Measured by Shear Wave Elastography | Normal Liver Stiffness | 13 Participants |
Secondary
Fibrotest
Fibrotest is a blood test that is a surrogate measure for hepatic fibrosis. F0 is normal. \>F0 predicts at least minimal fibrosis.
Time frame: Baseline, once
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Urea Cycle Disorders | Fibrotest | >F0 | 9 Participants |
| Urea Cycle Disorders | Fibrotest | F0 | 19 Participants |