[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"urea-cycle-disorders\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:urea-cycle-disorders":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,6,0,[8,43,71,100,121,143],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100643949","phase-1-a-phase-iii-open-label-safety-and-efficacy-study-of-lnpucdabe-in-patients-with-urea-cycle-disorders-100643949",false,"NCT07667387","A Phase I\u002FII Open-label Safety and Efficacy Study of LNP.UCD.ABE in Patients With Urea Cycle Disorders.","Master Protocol for a Phase I\u002FII Open-label Safety and Efficacy Study of LNP.UCD.ABE, a Lipid Nanoparticle-delivered Base Editing Therapy, in Patients With Urea Cycle Disorders Due to Variants Amenable to Corrective Editing by LNP.UCD.ABE","Inclusion Criteria:\n\n1. Diagnosis of a severe urea cycle disorder, in the judgement of the investigators;\n2. Molecular testing demonstrating homozygosity or compound heterozygosity for a disease-causing mutation in a urea cycle disorder gene (CPS1, OTC, ASS1, ASL, ARG, NAGS, or SLC25A15) that is targeted by a variant-specific version LNP.UCD.ABE;\n3. Current or historical biochemical testing consistent with a urea cycle disorder;\n4. At least one of the subject's alleles must be amenable to base editing by LNP.UCD.ABE, as assessed in vitro;\n5. A history of an ammonia level of ≥400 μmol\u002FL prior to age 12 months, unless a diagnosis was made prenatally and care was initiated immediately after birth. If the patient is taking an ammonia scavenger medication, their ammonia level may currently be in the normal range. If the patient is diagnosed prenatally, then personal history, family history, or analysis of mutations should indicate a high likelihood of a severe UCD;\n6. Subjects more than 8 weeks from the initial diagnosis of a severe UCD must have demonstrated a persistent need for dietary protein restriction and chronic administration of a nitrogen scavenger medication, and\u002For a recurrent hyperammonemic event, and\u002For a history of a hyperammonemic-induced seizure.\n7. Weight \\>3.5 kg at the time of screening;\n8. Legal guardian(s) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n\nExclusion Criteria:\n\n1. Abnormal liver function, electrolyte, coagulation, or blood count laboratory values thought not attributable to the underlying urea cycle disorder;\n2. Demonstrated need for urgent liver transplantation due to liver failure, in the opinion of the investigators;\n3. Participation in a prior gene therapy trial or participation in a trial of an investigational product in the last 12 months;\n4. History of liver transplantation;\n5. Any other diseases or conditions that the investigators would consider to pose unacceptable risk to the subject;\n6. Inability or unwillingness to comply with the visit schedule and study assessments;\n7. Any genetic variation in the causative urea cycle disorder gene that, in the opinion of the investigators, may decrease the potential efficacy of the drug product;\n8. History of severe hypersensitivity or anaphylaxis to polyethylene glycol (PEG)-containing products, such as PEG-containing vaccines or laxatives","ALL","24 Hours","5 Years",{"count":20,"type":21},7,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","This is a single-site Phase 1\u002F2 open-label umbrella clinical trial designed to evaluate the safety, tolerability, and efficacy of a single intravenous dose of LNP.UCD.ABE in 5 pediatric subjects with severe infantile-onset UCDs. This is a master clinical protocol in which subjects with a variant in a urea cycle disorder (UCD) gene (CPS1, OTC, ASS1, ASL, ARG, NAGS, or SLC25A15) that is demonstrated to be amenable to corrective editing by an adenine base editor (ABE) would be eligible for enrollment.",[28,29],"Urea Cycle Disorders","Carbamoyl-Phosphate Synthase I Deficiency","NOT_YET_RECRUITING","2026-06-26",{"date":33,"type":34},"2026-06-29","ACTUAL",{"date":36,"type":21},"2026-07",{"date":38,"type":21},"2028-07",{"name":40,"class":41},"Rebecca Ahrens-Nicklas","OTHER",1,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":16,"minAge":50,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":22,"phases":53,"briefSummary":55,"conditions":56,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":42},"100589368","at-home-ammonia-monitoring-of-inborn-errors-of-ammonia-metabolism-100589368","NCT06953505","At Home Ammonia Monitoring of Inborn Errors of Ammonia Metabolism","Pilot Study of At Home Ammonia Monitoring in Patients With an Inborn Error of Ammonia Metabolism","Inclusion Criteria:\n\n* Confirmed ammonia disorder such as\n\n  * Ornithine transcarbamylase deficiency\n  * Systemic primary carnitine deficiency\n  * Type I citrullinemia\n  * Argininosuccinic aciduria\n  * Isolated methylmalonic acidemia\n  * Type II citrullinemia\n  * Propionic acidemia\n  * Isovaleric acidemia\n  * Multiple acyl-CoA dehydrogenase deficiency\n  * Pyruvate carboxylase deficiency\n  * Argininemia (arginase deficiency)\n  * Carbamoyl phosphate synthase I deficiency\n  * Dihydrolipoamide dehydrogenase deficiency\n  * Lysinuric protein intolerance\n  * Hyperornithinemia-hyperammonemia-homocitrullinuria\n  * Carnitine-acylcarnitine translocase deficiency\n  * Carbonic anhydrase VA deficiency\n  * N-acetyl glutamate synthetase deficiency\n* English Literacy\n\nExclusion Criteria:\n\n* Incarcerated\n* Presence of a non-inborn error of metabolism medical condition associated with abnormal ammonia metabolism (e.g., end stage liver disease).\n* Unable to read in English","12 Years",{"count":52,"type":21},30,[54],"NA","The goal of this observational study is to learn if people with certain ammonia metabolism disorders will measure their ammonia levels at home.\n\nThe main question it aims to answer is:\n\n• Will participants measure their ammonia every day?\n\nParticipants will be asked to:\n\n* Attend two in-person study visits at the clinic.\n* Measure temperature, heart rate, and blood oxygen every day.\n* Complete a short survey every day.\n* Measure ammonia every day.",[28,57,58,59],"Organic Acidemias","Fatty Acid Oxidation Disorder","Ammonia; Metabolic Disorder","RECRUITING","2026-05-21",{"date":63,"type":34},"2026-05-27",{"date":65,"type":34},"2025-09-23",{"date":67,"type":21},"2027-08",{"name":69,"class":70},"Sequitur Health Corp.","INDUSTRY",{"id":72,"slug":73,"hasResults":11,"nctId":74,"briefTitle":75,"officialTitle":76,"acronym":4,"eligibilityCriteria":77,"healthyVolunteers":11,"sex":16,"minAge":78,"maxAge":79,"enrollmentInfo":80,"targetDuration":4,"studyType":82,"phases":4,"briefSummary":83,"conditions":84,"keywords":85,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":95,"leadSponsor":97,"locationsCount":99},"100585566","a-clinical-study-of-glycerol-phenylbutyrate-in-chinese-patients-with-urea-cycle-disorders-100585566","NCT06904027","A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders","A Single-arm, Prospective, Multi-center Post-market Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders","Inclusion Criteria:\n\n1. Male or female aged 0-18 years;\n2. Subject and\u002For subject's legally authorized representative willing to follow the therapeutic regimen, dietary management and visit plan of the study, and voluntarily signing informed consent form;\n3. Patients with the following subtypes of UCD: Carbamoyl phosphate synthetase I deficiency, Ornithine translocase deficiency, citrullinemia type I, argininosuccinic aciduria, argininemia, and hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome;\n4. Patients planned to use glycerol phenylbutyrate who have not used it in past 3 months (including at the time of 3 months);\n5. Men with fertility and women of childbearing potential (with menstruation) who are willing to take effective contraceptive measures during the period from the date of signing the informed consent to 1 months after the last dose of the study drug, such as abstinence, condoms, intra-uterine contraceptive devices, and double barrier methods (such as condoms + contraceptive diaphragms). Pregnancy test results must be negative for women of childbearing age within ≤ 7 days before the initial administration of study drug.\n\nExclusion Criteria:\n\n1. Hypersensitivity to any of the active ingredient, including phenylbutyrate (PBA), phenylacetate acid (PAA) and phenylacetyl glutamine (PAGN), or excipients;\n2. Use of any drug known to significantly affect renal clearance (such as probenecid) or increase protein catabolism (such as corticosteroids) or other drugs known to increase blood ammonia levels (such as valproate) within 24 h before the first administration;\n3. Use of other nitrogen-scavenging agent at the same time after enrollment, such as sodium phenylbutyrate and sodium benzoate;\n4. Pregnant or breastfeeding females.\n5. Other reasons, in the opinion of the investigator, that may affect the patient's compliance and safety in participating in the study.","0 Years","18 Years",{"count":81,"type":21},40,"OBSERVATIONAL","Urea cycle disorders (UCD) are rare diseases in China, would lead to high mortality and disability, which require long-term management due to the recurrent symptoms. This multi-center, prospective, single-arm study was designed to assess the efficacy and safety of Glycerol Phenylbutyrate for Chinese pediatric patients with UCD, to provide the additional references and treatment options for Chinese UCD patients, and enhance the clinical management of UCD in China. This study primarily observes patients with UCD who are on long-term treatment with glyceryl phenylbutyrate, the total planned observation period is 5 years.",[28],[86,87,88,89],"Chinese","Pediatric patients","Urea cycle disorders","Glycerol phenylbutyrate","2026-04-23",{"date":92,"type":34},"2026-04-27",{"date":94,"type":34},"2025-12-09",{"date":96,"type":21},"2031-07",{"name":98,"class":41},"Tongji Hospital",5,{"id":101,"slug":102,"hasResults":11,"nctId":103,"briefTitle":104,"officialTitle":104,"acronym":4,"eligibilityCriteria":105,"healthyVolunteers":106,"sex":16,"minAge":4,"maxAge":4,"enrollmentInfo":107,"targetDuration":4,"studyType":22,"phases":109,"briefSummary":110,"conditions":111,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":112,"lastUpdatePostDateStruct":113,"startDateStruct":115,"completionDateStruct":117,"leadSponsor":119,"locationsCount":42},"100490864","ureagenesis-analysis-in-healthy-subjects-and-in-urea-cycle-disorder-patients-100490864","NCT05671666","Ureagenesis Analysis in Healthy Subjects and in Urea Cycle Disorder Patients","Inclusion Criteria:\n\n* healthy subjects at any age and given written informed consent\n* subjects with a UCD confirmed by genetic or enzymatic diagnostics at any age and given written informed consent\n\nExclusion Criteria:\n\n* healthy subjects with acute and chronic disease requiring treatment of any kind\n* pregnant or lactating women.\n* UCD patients with acute and chronic (other than her\u002Fhis UCD) disease requiring treatment\n* UCD patients in which intake of carglumic acid cannot be stopped for 24 hours prior to the test",true,{"count":108,"type":21},100,[54],"Urea cycle disorders (UCDs) are dramatic congenital inherited metabolic disorders. There is no cure. Many novel therapeutic approaches are currently being developed, which hopefully will change the current situation. Testing the efficacy of such new therapies in patients is a challenge, because many clinical parameters are influenced by several disturbances and biochemical parameters are often not very specific.\n\nThe measurement of ureagenesis is a tool to analyze the entire function of the urea cycle in a single test. This is more meaningful for the characterization of UCD patients than the analysis of single metabolites or enzymes. Therefore, the test will be important to evaluate current and future novel therapies.\n\nThe term \"ureagenesis\" means \"production of urea\", which is the main task of the urea cycle. This total urea production can be measured with a \"tracer\" (in this case a stable ammonium chloride isotope). This tracer is non-radioactive and non-toxic. It is for example used as an unmarked substance in cough syrup, diuretic drugs and as food additive. Thus, the tracer does not pose a risk to the participant, especially since only a very low dose is applied.\n\nThe investigators will analyze specific substances from the urea cycle (namely \\[15N, 14N\\] urea and several \\[15N\\] amino acids) that are produced during the test and compare them with results from healthy people. Venous and capillary blood will be sampled at 15 to 30 minutes intervals up to 2 hours after administration of the stable isotope tracer. The maximum test duration is 5 hours.\n\nThis project is being carried out at one site, namely the University Children's Hospital in Zurich.\n\nThis project is being carried out under Swiss law. The responsible Ethics Committee has reviewed and approved the study.",[28],"2026-01-05",{"date":114,"type":34},"2026-01-08",{"date":116,"type":34},"2019-10-31",{"date":118,"type":21},"2035-12-31",{"name":120,"class":41},"University Children's Hospital, Zurich",{"id":122,"slug":123,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":125,"acronym":126,"eligibilityCriteria":127,"healthyVolunteers":106,"sex":16,"minAge":128,"maxAge":129,"enrollmentInfo":130,"targetDuration":4,"studyType":82,"phases":4,"briefSummary":132,"conditions":133,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":135,"startDateStruct":137,"completionDateStruct":139,"leadSponsor":141,"locationsCount":42},"100280810","neuroimaging-and-neuropsychological-outcomes-in-urea-cycle-disorders-100280810","NCT02935283","Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders","UCD","Inclusion Criteria:\n\nInclusion criteria for group 1:\n\n1. Confirmed diagnosis of ornithine transcarbamylase deficiency (OTCD) by genetic analysis (genotype) and\u002For enzyme analysis with at least a single episode of HA hyperammonemic (HA) encephalopathy\n2. Ability to undergo MRI without sedation\n3. Ages 7 - 50 years\n4. Ability to provide informed consent or assent to the procedures\n5. Healthy controls (age and gender matched)\n\nInclusion criteria for group 2:\n\n1. Males and females with a UCD who are having an acute metabolic crisis, with ammonia levels between 100-300 µM\n2. Subjects must be awake, and not comatose and able to maintain patent airway on their own and in the opinion of the examining physician, medically stable without risk for acute decompensation and must continue to be stable based on visual contact, vital sign measurement and voice contact with subjects while in the scanner\n3. Age range 7-30 years\n4. Able to undergo neuroimaging safely (i.e. without ferromagnetic devices)\n5. Sexually active female of childbearing potential must agree to urine pregnancy test\n6. Admitted to the hospital for treatment of HA at one of the 4 sites for this study\n7. Can be subjects who were originally enrolled in aim 1 who then have HA (they will cross over to aim 2)\n\nInclusion criteria for group 3\n\n1. Confirmed diagnosis of arginosuccinate ASSD, and ASLD by genotype and\u002For enzyme analysis or healthy age and gender matched control\n2. Ability to undergo MRI without sedation\n3. Age 7 - 30 years\n4. Able to provide informed consent or assent to the procedures\n\nExclusion Criteria:\n\nExclusion Criteria for group 1:\n\n1. Inability to undergo MRI without sedation\n2. Metal implants, including orthodontic braces\n3. Other health conditions contra-indicated in MRI\n4. Medically unstable at time of scheduled research visit\n5. Unable to provide informed consent or assent to the procedures\n\nExclusion criteria for group 2:\n\n1. Ammonia level \\> 300 µM, or \\\u003C100 µM\n2. Presence of coma and\u002For inability to maintain a patent airway\n3. Age \\\u003C7 or \\>30 years\n4. Subject with ferromagnetic device that precludes safe MRI imaging\n5. Pregnant female\n6. Unstable medically, at risk for decompensations\n7. Combative, or severely neurologically compromised irrespective of ammonia level and showing declining medical status in the scanner based on visual, voice contact and electronic HR monitoring.\n\nSubjects must be awake, and not comatose and able to maintain patent airway on their own\n\nExclusion criteria for group 3:\n\n1. Inability to undergo MRI without sedation\n2. Metal implants, including orthodontic braces\n3. Other health conditions contra-indicated for MRI\n4. Medically unstable at time of scheduled research visit\n5. Unable to provide informed consent or assent","7 Years","50 Years",{"count":131,"type":21},56,"In proximal urea cycle disorders (UCD), particularly ornithine transcarbamylase deficiency (OTCD), hyperammonemia (HA) causes increased brain glutamine (Gln) which perturbation is thought to be at the core of the neurological injury. In contrast, in distal UCD such as citrullinemia (argininosuccinate synthetase deficiency; (ASSD) and argininosuccinic aciduria (argininosuccinate lyase deficiency); (ASLD) cognitive impairment and neuropsychiatric disease are common even in the absence of acute HA. As a consequence, both citrulline and argininosuccinate (ASA) or their metabolic products have been implicated as neurotoxic. In this project the investigators will use state-of- the-art neuroimaging and neuropsychological methods to investigate whether patients with OTCD have chronically elevated brain Gln and reduced myo-inositol (mI) levels that correlate with regional brain structural abnormalities and neurocognitive dysfunction. The researchers will further investigate whether during an acute episode of HA elevated brain Gln and decreased mI levels correlate with the magnitude of cytotoxic edema and whether a Gln\u002FmI ratio threshold can be identified at which the cytotoxic edema is followed by cell loss. Finally, the researchers will investigate whether regions of brain damage in ASSD and\u002For ASLD are distinct from those in OTCD and compare brain Gln levels in ASSD and ASLD in the absence of HA to those in OTCD. The investigators will also seek to determine if brain citrulline and ASA can be identified in the brains of patients with distal UCD and whether they correlate with brain abnormalities seen in MRI and neuropsychological testing. This project will elucidate the chronology of brain pathology both in acute hyperammonemia and chronic UCD and whether, proximal and distal UCD differ in their pathophysiology of brain damage.",[28],"2024-06-22",{"date":136,"type":34},"2024-06-25",{"date":138,"type":4},"2016-08",{"date":140,"type":21},"2025-12",{"name":142,"class":41},"Children's National Research Institute",{"id":144,"slug":145,"hasResults":11,"nctId":146,"briefTitle":147,"officialTitle":147,"acronym":4,"eligibilityCriteria":148,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":4,"enrollmentInfo":149,"targetDuration":4,"studyType":82,"phases":4,"briefSummary":151,"conditions":152,"keywords":155,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":158,"lastUpdatePostDateStruct":159,"startDateStruct":161,"completionDateStruct":163,"leadSponsor":164,"locationsCount":166},"100075501","longitudinal-study-of-urea-cycle-disorders-100075501","NCT00237315","Longitudinal Study of Urea Cycle Disorders","Inclusion Criteria:\n\n* Diagnosis of NAGS deficiency, defined as the detection of a pathogenic mutation, and\u002For decreased (less than 20 % of control) NAGS enzyme activity in liver ,and\u002For hyperammonemia and first degree relative meets at least one of the criteria for NAGS deficiency\n* Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I enzyme activity in liver, and\u002For an identified pathogenic mutation, and\u002For hyperammonemia and first degree relative meets at least one of the criteria for CPS I deficiency\n* Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation, and\u002For less than 20% of control of OTC activity in the liver, and\u002For elevated urinary orotate (greater than 20 uM\u002FmM) in a random urine sample or after allopurinol challenge test, and\u002For hyperammonemia and first degree relative meets at least one of the criteria for OTC deficiency\n* Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to 10-fold elevation of citrulline in plasma, and\u002For decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue, and\u002For identification of a pathogenic mutation in the AS gene, and\u002For hyperammonemia and first degree relative meets at least one of the criteria for AS Deficiency\n* Diagnosis of AL deficiency (Argininosuccinic Aciduria, ASA), defined as the presence of argininosuccinic acid in the blood or urine, and\u002For decreased AL enzyme activity in cultured skin fibroblasts or other appropriate tissue, and\u002For identification of a pathogenic mutation in the AL gene, and\u002For hyperammonemia and first degree relative meets at least one of the criteria for AL Deficiency\n* Diagnosis of ARG deficiency (Hyperargininemia), defined as a greater than or equal to 5-fold elevated arginine levels in the blood, and\u002For decreased arginase enzyme levels in red blood cells or other appropriate tissue, and\u002For identification of a pathogenic mutation in the ARG gene, and\u002For hyperammonemia and first degree relative meets at least one of the criteria for ARG Deficiency\n* Diagnosis of HHH Syndrome or ORNT deficiency, defined as a greater than or equal to 5-fold elevated plasma ornithine and homocitrulline levels in the urine, and\u002For a pathogenic mutation, and\u002For less than 20% residual labeled ornithine incorporation into protein in cultured fibroblasts, and\u002For hyperammonemia and first degree relative meets at least one of the criteria for HHH Syndrome or ORNT Deficiency\n* Diagnosis of CITR deficiency (Citrullinemia Type II), defined as elevated citrulline levels in the blood and a pathogenic mutation and\u002For hyperammonemia and first degree relative meets criteria for CITR Deficiency\n* Pending diagnosis of a UCD (UCD highly likely), defined as laboratory values highly suggestive of a UCD with symptomatic hyperammonemic episodes but without a verifiable diagnosis\n\nExclusion Criteria:\n\n* Hyperammonemia caused by an organic academia, lysinuric protein intolerance, mitochondrial disorder, congenital lactic academia, fatty acid oxidation defects, or primary liver disease\n* Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)",{"count":150,"type":21},1500,"Urea cycle disorders (UCD) are a group of rare inherited metabolism disorders. Infants and children with UCD commonly experience episodes of vomiting, lethargy, and coma. The purpose of this study is to perform a long-term analysis of a large group of individuals with various UCDs. The study will focus on the natural history, disease progression, treatment, and outcome of individuals with UCD.",[153,154,28],"Brain Diseases, Metabolic, Inborn","Amino Acid Metabolism, Inborn Errors",[156,157],"Urea","Inherited metabolic disorders","2024-02-10",{"date":160,"type":34},"2024-02-13",{"date":162,"type":34},"2006-02",{"date":36,"type":21},{"name":165,"class":41},"Andrea Gropman",15]