Ornithine Transcarbamylase Deficiency

Urea cycle disorders UCD are rare diseases in China that can cause high mortality and disability, requiring long-term management due to recurring symptoms. This multi-center, prospective, single-arm study aims to evaluate the safety and effectiveness of Glycerol Phenylbutyrate in Chinese children with UCD. The goal is to provide more treatment options and improve clinical care for these patients in China. The study plans a total observation period of five years for patients on long-term treatment with this medication. The study involves 40 children aged from birth to 18 years diagnosed with various types of UCD, including carbamoyl phosphate synthetase I deficiency and others. Participants will receive Glycerol Phenylbutyrate oral liquid, with dosing based on body surface area and divided into multiple daily doses taken with meals. The study includes scheduled clinic visits at 1 month and 3 months after enrollment, followed by visits every 6 months up to 5 years. During these visits, researchers collect data on adverse events, dosage changes, hyperammonemic crises, and blood ammonia levels. Participants will undergo regular assessments including blood tests for ammonia and biochemistry, growth measurements height, weight, head circumference, and neurocognitive evaluations at specified intervals. The primary outcome is the mean blood ammonia level at 3 months after enrollment. Secondary outcomes include ammonia levels at multiple timepoints, frequency of crises, growth data, dosage adjustments, and various neurodevelopmental scores measured annually. This comprehensive follow-up aims to monitor safety, treatment effects, and overall development throughout the five-year period.

Researchers are evaluating the safety and pharmacodynamics of multiple doses of ARCT-810, an investigational drug, in adolescents and adults with Ornithine Transcarbamylase OTC deficiency. This Phase 2a, open-label study aims to better understand how ARCT-810 works and its safety profile in people aged 12 years and older who have this condition. Participants must have a documented diagnosis of OTC deficiency and be medically managed with a stable diet and supplements. Participants will receive up to five intravenous infusions of ARCT-810 every two weeks, following a diet stabilization period of at least four weeks. The study includes three different dose levels, and dose escalation or cohort expansion may occur after three participants complete each dose level. Participants will continue their usual clinical management for OTC deficiency throughout the study. During the study, participants will have clinic visits at screening and on Days 1, 15, 29, 36, 43, 57, 60, 71, and 85. Researchers will monitor adverse events, pharmacokinetics, fasting plasma ammonia, plasma glutamine, and stable isotope ureagenesis assay values. The primary outcome is the incidence, severity, and dose relationship of adverse events by Day 85. The total participation duration includes ongoing assessments up to Day 85 to evaluate safety and drug effects.

Researchers are collecting both short-term and long-term safety information from adults and children treated for hyperammonemia caused by Methylmalonic Acidemia MMA and Propionic Acidemia PA. This observational study focuses on patients receiving Carbaglu4 as part of their usual medical care, aiming to understand the effects of this treatment in real-world settings. Participants will be treated according to standard medical practices, receiving Carbaglu4 as prescribed by their doctors. The study gathers data on patients treated either as outpatients or inpatients, including details about Carbaglu4 dosing, other treatments for hyperammonemia like diet and protein management, and pregnancy-related outcomes. Data collection continues for about one year after stopping Carbaglu4. During the study, researchers will review plasma ammonia levels and record any adverse events, including their frequency and severity. They will also collect information on pregnancy outcomes and effects on infants up to one year old. No additional treatments or interventions are administered beyond routine care. This allows for monitoring safety and developmental outcomes over time in this patient group.

Ornithine Transcarbamylase OTC deficiency is a genetic metabolic disorder mainly affecting male babies, caused by a defect in a liver enzyme that helps remove ammonia from the blood. This condition can lead to high ammonia levels resulting in serious brain damage, coma, or death, especially in severe cases presenting shortly after birth. The study is a Phase 123, open-label, multicenter trial designed to assess the safety, effectiveness, and dosing of ECUR-506 in male infants with neonatal-onset OTC deficiency. ECUR-506 is an investigational gene editing therapy that delivers a working OTC gene and an editing enzyme using a virus-based delivery system called adeno-associated virus AAV. The treatment is given as a single intravenous infusion at one of three dose levels low, intermediate, or high. Participants receive only one dose during the study to evaluate safety and response. During the study, participants will be monitored for 24 weeks after receiving the infusion. Researchers will assess safety through physical exams, vital signs, neurological exams, blood and urine tests, ECGs, and adverse events. They will also evaluate effectiveness by tracking episodes of high ammonia, hospitalizations, liver transplant requirements, survival, and clinical responses. This close monitoring aims to understand how the gene therapy works and its impact on the condition.

Researchers are investigating whether people with certain inherited ammonia metabolism disorders can successfully measure their ammonia levels daily at home. The study focuses on understanding participants ability to regularly use a new ammonia measurement device and complete daily health monitoring. This research aims to improve management of conditions like urea cycle disorders and other metabolic diseases that affect ammonia processing in the body. Participants will use an investigational ammonia device that measures total ammonia from a single drop of blood using a reusable instrument and single-use cartridge. They will be asked to measure their ammonia levels daily, along with temperature, heart rate, and blood oxygen. The study includes two in-person clinic visits and an optional extension period, with monitoring lasting approximately 240 days, extendable by another 120 days. During the study, participants will complete daily surveys and record their health measurements to help researchers track adherence and gather data. The main outcome measured is the percentage of daily ammonia tests completed. Researchers will also analyze descriptive statistics and correlations over the study period to better understand home monitoring feasibility and patterns. Participants involvement lasts around 8 months, with optional continued participation for an additional 4 months.

Researchers are studying how the brain functions in people with urea cycle disorder UCD while they perform driving tasks of varying difficulty. This observational study compares brain activity during simulated driving between individuals with UCD and healthy volunteers, aiming to understand differences in thinking and attention. The study uses functional near-infrared spectroscopy fNIRS to measure brain oxygen levels in specific areas during these tasks. Participants will wear a soft cap equipped with fNIRS sensors that monitor oxygen changes in different brain regions such as the prefrontal, parietal, and occipital areas while they complete a driving simulation. The study includes both individuals diagnosed with UCD and healthy control participants matched by age and sex. All activities, including neurological exams, questionnaires about health and driving habits, and cognitive tests, will be conducted in one visit. Participants will have their medical history reviewed and complete simple memory and attention tests to assess cognitive skills. Brain oxygenation levels will be recorded during the driving task to evaluate brain function. The study measures changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations in different brain regions in both groups. All study procedures, including assessments and simulator use, take place during a single day of enrollment.

Ornithine transcarbamylase deficiency OTCD is a rare inherited liver disorder that prevents the body from maintaining normal ammonia levels, leading to dangerous ammonia buildup in the blood. This condition can cause life-threatening episodes called hyperammonaemic decompensations, which may result in vomiting, movement problems, lethargy, coma, and impaired neurological development in children. Current treatments include drugs to reduce ammonia and low-protein diets, but these do not always prevent these dangerous episodes. Liver transplantation can be life-saving but may be delayed, risking further neurological harm. The trial is testing a gene therapy called AAVLK03hOTC, designed to target the liver and enable production of the missing OTC enzyme. The study involves escalating doses given by intravenous infusion in children from birth to 16 years old, with groups receiving low to high doses and an additional group receiving the dose with the best safety and efficacy balance. This gene therapy aims to help the liver function normally, reduce dangerous ammonia buildups, and act as a bridge to liver transplant. Participants will be closely monitored for safety and effectiveness for at least 12 months after infusion, including tracking any adverse events. Long-term follow-up of up to four years will assess ongoing safety. Researchers will regularly assess ammonia levels, liver function, and overall health to understand the gene therapys impact on managing OTCD. The study is open-label and involves multiple centers, aiming to provide important information on this new treatment option for children with OTCD.

Urea cycle disorders UCDs are common inherited liver metabolism conditions. Improved diagnosis and treatments have increased survival rates, revealing some long-term liver complications like dysfunction and fibrosis in some patients. These liver issues vary depending on the specific metabolic defect causing the disorder. The study aims to better understand these complications by examining liver tissue samples from individuals diagnosed with any UCD. This research involves reviewing past medical records and prospectively collecting liver tissue samples from patients with confirmed UCD diagnoses. It includes individuals who have had or are planning to have liver biopsies or transplants. This observational study is conducted across multiple centers within the Urea Cycle Disorders Consortium, including Baylor College of Medicine and Childrens National Medical Center. Participants liver samples will be evaluated for fibrosis, fat accumulation steatosis, and glycogen buildup hepatic glycogenosis. Researchers will analyze histopathology reports, biopsy slides, and tissue blocks to identify these outcomes. The study collects data retrospectively and prospectively, tracking histological changes to better understand liver complications in UCD. Participation involves no interventions and focuses on reviewing existing and new liver tissue findings until study completion in June 2026.

Researchers are conducting a long-term follow-up study lasting 14.5 years to assess the safety and lasting effects of an investigational product IP used in previous iECURE studies. The study also aims to gather ongoing natural disease information from participants who enrolled but were not treated with the IP. Participants continue their usual medical care prescribed by their doctors throughout the study. This observational study does not provide any investigational treatment. Instead, it follows two groups those who received the IP in earlier iECURE studies and those who were enrolled but not dosed. No new drug or therapy is given as part of this follow-up. Participants maintain their prescribed standard care while researchers collect data over time. Participants will be monitored regularly for safety, growth changes, and other health measures over 14.5 years. The study collects information on adverse events, changes in height and weight, urinalysis results, and detailed laboratory tests including vector clearance in blood, saliva, urine, and feces. Researchers also track serious health events related to the disease, hospitalizations, and survival outcomes. This comprehensive follow-up aims to provide valuable long-term data on participants health and treatment effects.

This research focuses on acute neonatal hyperammonemia, a serious condition linked to poor neurological outcomes and high mortality in newborns. Researchers aim to validate a user-friendly, widely applicable algorithm that tailors treatment based on kinetic modeling. This approach is designed to help medical staff personalize care for babies with severe hyperammonemia by predicting treatment times and dialysis settings specific to each patient. The study evaluates an algorithm that uses a simple spreadsheet to calculate dialysis protocols. It considers factors like patient body weight, blood flow rate, and ammonia concentration to tailor treatment. The algorithm is based on measurements of ammonia levels before and after dialysis, allowing precise calculation of dialyzer clearance and treatment duration. This method aims to improve the management of acute neonatal hyperammonemia with practical, individualized guidance. Participants under one year old with severe neonatal hyperammonemia undergoing acute hemodialysis will be involved. The study will monitor serum ammonium levels over one year as the primary outcome, along with the removal of sodium benzoate and L-arginine as secondary outcomes. Data collection includes ammonia measurements during dialysis sessions to assess the algorithms accuracy and effectiveness in guiding treatment plans.