Manipulating the Gut Microbiome Study
Urea Cycle Disorder
About this trial
This is an interventional treatment trial for Urea Cycle Disorder focused on measuring CPSI deficiency, OTC Deficiency, AS Deficiency, AL Deficiency
Eligibility Criteria
Inclusion Criteria:
- For Group 1 (healthy adults):
- Ages 18-60 years
- Compliant with receiving medications orally and intravenously
- Compliant with providing blood and urine samples
For Group 2 (adult UCD patients):
- Ages 18-60 years
- Compliant with receiving medications orally and intravenously
- Compliant with providing blood and urine samples
Established diagnosis of CPSD, OTCD, ASSD or ASLD as follows:
- Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I enzyme activity in liver or an identified pathogenic mutation
- Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation, linkage analysis in an affected family, less than 20% of control of OTC activity in the liver, or elevated urinary orotate (greater than 20 uM/mM) in a random sample or following allopurinol loading with absence of argininosuccinic acid
- Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to 10-fold elevation of citrulline in plasma, decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue, or identification of a pathogenic mutation in the AS gene
- Diagnosis of AL deficiency (Argininosuccinic Aciduria, ASA), defined as the presence of argininosuccinic acid in the blood or urine, decreased AL enzyme activity in cultured skin fibroblasts or other appropriate tissue, or identification of a pathogenic mutation in the AL gene
Exclusion Criteria:
- For both Group 1 and Group 2:
- Current or prior Helicobacter pylori infection
- Chronic gastrointestinal illness (e.g., inflammatory bowel disease)
- Chronic renal failure
- Taking probiotic medications within a week of study start date
- Currently pregnant or lactating. Documentation of a negative pregnancy test within a week prior to testing is required, unless pre-menarchal or menopausal, experiencing menses that week, or other circumstances which preclude pregnancy (e.g. hysterectomy).
- Presence of acute infection at the time of inclusion
- Participation in any other clinical interventional trial or received experimental medication within the last 30 days
- Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at an additional risk by participating in this study
Sites / Locations
- Children's National Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Acetohydroxamic Acid Oral Tablet then No Intervention
No Intervention then Acetohydroxamic Acid Oral Tablet
Participants receive a single oral dose of 60 mg/kg acetohydroxamic acid (rounded to the nearest 250 mg) in the fasted state on the morning of the study. After completion of the 4-h study, participants then enter a wash-out period of 3 days. Participants then completed an identical 4-h study in the fasted state without acetohydroxamic acid.
Participants completed a 4-h study in the fasted state without acetohydroxamic acid. 3 days later, participants then completed an identical 4-h study in the fasted state, after having received a single oral dose of 60 mg/kg acetohydroxamic acid (rounded to the nearest 250 mg).