Urea Cycle Disorders (UCD) Clinical Trials and Treatments

Urea Cycle Disorders result from mutations in genes encoding any of the 8 enzymes or transporter proteins in the urea cycle: carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), N-acetylglutamate synthase (NAGS), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase 1 (ARG1), and 2 transporters, the mitochondrial ornithine transporter 1 (ORNT1) and citrin. Together they carry out the steps that turn ammonia and CO2 into urea. Enzyme deficiency prevents ammonia disposal, leading to hyperammonemia with toxic effects on the CNS.

The most common symptoms of Urea Cycle Disorders include Neonatal presentation: poor feeding, vomiting, lethargy progressing to coma, Hyperammonemic crisis: acute neurological deterioration, confusion, seizures, Protein intolerance and aversion to high-protein foods, Developmental delay and intellectual disability if untreated, Behavioral problems and attention difficulties, among others. About 1 in 35,000 births in the United States, based on newborn screening and registry data (Summar et al., 2013); Ornithine Transcarbamylase (OTC) deficiency is most common form. Symptoms can range from mild to severe and may vary between individuals.

Trial Friend lists all active clinical trials for Urea Cycle Disorders from ClinicalTrials.gov, with eligibility criteria translated into plain English. Patients can filter by trial phase and recruitment status, search by location, and use the Match Me tool to score trials against their profile. Research in Urea Cycle Disorders is focused on reducing toxic ammonia levels and restoring normal metabolism through multiple complementary strategies. Ammonia-lowering medications and improved pharmacologic ammonia scavenging agents are being refined in trials.

Yes. As of October 21, 2026, 4 FDA-approved medicines have a current label that names Urea Cycle Disorders: Carbaglu (carglumic acid); Glycerol Phenylbutyrate (glycerol phenylbutyrate oral); Pheburane (sodium phenylbutyrate); and Sodium phenylacetate and Sodium benzoate. Corticosteroids and immune globulins count once each.

Urea Cycle Disorders is caused by variants in any of many genes, most often OTC, ASS1, ASL, CPS1, ARG1 and NAGS. Eight genes (six enzymes plus the SLC25A15 and SLC25A13 transporters) cause urea cycle disorders; OTC deficiency is the most common and is X-linked, so heterozygous females can be symptomatic.

It follows X-linked (OTC) or autosomal recessive (all others) inheritance. About 1 in 35,000 births in the United States, based on newborn screening and registry data (Summar et al., 2013); Ornithine Transcarbamylase (OTC) deficiency is most common form. A multigene panel identifies the cause in most families.

Yes. Urea Cycle Disorders can be caused by variants in many different genes (OTC, ASS1, ASL, CPS1, ARG1 and NAGS are among the most common), so testing is usually a multigene panel or exome sequencing rather than one gene at a time. Eight genes (six enzymes plus the SLC25A15 and SLC25A13 transporters) cause urea cycle disorders; OTC deficiency is the most common and is X-linked, so heterozygous females can be symptomatic.

It follows X-linked (OTC) or autosomal recessive (all others) inheritance.

Knowing the exact gene matters: it decides which trials a patient qualifies for and which relatives should be tested. The labs currently offering the test are listed in the Genetic Testing section of this page, pulled live from the NIH Genetic Testing Registry. A genetic counselor can help interpret the result and decide which relatives should be tested.

Eligibility for Urea Cycle Disorders clinical trials depends on factors like age, diagnosis, treatment history, and overall health. Each trial sets its own inclusion and exclusion criteria. Trial Friend translates these requirements from medical language into plain English so patients can review them more easily. The Match Me tool can score your profile against active trials to help identify studies that may be a fit.

Participating in a Urea Cycle Disorders clinical trial typically involves scheduled visits, medical tests, and close monitoring by a research team. Depending on the study phase, you may receive an investigational treatment, a placebo, or the current standard of care. Trials may last from a few weeks to several years. Study participation is voluntary, and you can withdraw at any time.