Urea Cycle Disorder

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 effects of Diaberine, a berberine-based nutraceutical, on blood sugar regulation and metabolism in adults with metabolism disorder. This randomized, triple-blind, placebo-controlled trial will study 80 participants aged 18 to 70 over 24 weeks to assess how well this dietary supplement may aid in these health areas. Participants will be randomly assigned to one of two groups. One group will take Diaberine capsules containing Vitamin B12, berberine, magnesium citrate, cinnamon bark extract, chromium, and other ingredients three times daily, 15 minutes before meals. The other group will take placebo capsules with similar appearance but without the active ingredients. Both treatments will continue for 24 weeks with regular monitoring. During the study, participants will have their blood sugar regulation and metabolism measured at baseline, week 12, and week 24. Additionally, quality of life and weight changes will be tracked at multiple points throughout the 24 weeks. Participants will be monitored through questionnaires, blood tests, and weight assessments to evaluate the supplement's effects and tolerance over time.

Researchers are studying how metabolism relates to body composition and body surface area (BSA) in a wide range of people, including healthy individuals and those with conditions like diabetes, obesity, kidney disease, or cancer. They aim to find more accurate ways to measure metabolism and understand how measured BSA compares to estimates based on height and weight. This observational natural history study is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Participants will spend 2 days and 1 night in the hospital for testing. They will provide medical history and information about their activity, diet, and lifestyle, and consume a special diet during the stay. Tests include lying under a clear hood to measure breath gases, body scanning while lying down and standing, measuring electrical signals through the body, hand strength tests, and providing blood and urine samples after drinking salty water. Participants may return for up to 8 such visits per year, with at least 2 weeks between visits. During the study, researchers will monitor resting energy expenditure, body composition, and BSA through these tests and questionnaires. They will track differences between measured and predicted BSA and how BSA relates to energy use. Safety and ability to complete tests are monitored, and the total participation time depends on the number of visits. This detailed assessment helps understand metabolism across health and disease states.

Researchers are studying the safety and effectiveness of a single dose of nexiguran ziclumeran (NTLA-2001) compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score +7 (mNIS+7) over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants' nerve health and overall well-being.

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 affecting the liver's ability to detoxify ammonia, often causing severe neurological damage, coma, or death shortly after birth. This condition is more common and severe in male babies. Researchers are studying ECUR-506, an investigational gene editing therapy, to evaluate its safety, tolerability, and effectiveness in treating male infants under 9 months old with neonatal-onset OTC deficiency in a Phase 1/2/3 open-label trial. ECUR-506 delivers a functional OTC gene and a gene for an editing enzyme using a viral vector through a single intravenous infusion. The study tests three dose levels: low, intermediate, and high, each given once by IV infusion. Participants receive only one dose and are monitored over time to assess the impact of this gene editing treatment on their condition. During the study, babies will be closely monitored for safety and response through physical exams, neurologic assessments, vital signs, blood tests, urinalysis, and ECGs at scheduled times up to 24 weeks after infusion. Researchers will track adverse events, ammonia levels, hospitalizations, and other clinical outcomes such as survival and need for liver transplant. The total participation period covers about 24 weeks of follow-up to evaluate ECUR-506's effects and safety.

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 evaluating a reduced-intensity preparative regimen for hematopoietic stem cell transplantation in children and young adults with non-malignant disorders. This approach aims to maximize immune suppression without using radiation or high-dose chemotherapy, intending to reduce early and late toxicities. The study also focuses on preventing complications like graft-versus-host disease (GVHD) by using specific prophylaxis methods during matched and mismatched donor transplants from bone marrow and cord blood sources. The trial includes different groups based on the type of non-malignant disorder and the donor match. Treatments involve drug regimens such as Campath, Fludarabine, Melphalan, and sometimes Thiotepa, given before transplantation to prepare the body. GVHD prevention drugs like Tacrolimus, Cyclosporine, Mycophenolate mofetil (MMF), Abatacept, and Methotrexate are administered on specific days before and after the stem cell infusion, which occurs on day 0. Participants will be closely monitored for donor cell engraftment and major toxicities within the first 100 days after transplant. Assessments include measuring blood counts for neutrophil and platelet recovery, tracking acute and chronic GVHD occurrences up to two years post-transplant, and evaluating immune recovery one year after transplant. Overall and disease-free survival will also be followed for two years. The study spans from preparative treatment through long-term follow-up, with safety and effectiveness monitored at regular intervals.

Researchers are exploring how the stress of caregiving affects the health and well-being of adults who care for people with chronic medical conditions. This observational study aims to understand the social, psychological, behavioral, and biological factors involved in caregiving over time, including during and after the death of the care recipient. The study includes caregivers of various chronic conditions such as inherited metabolic disorders, undiagnosed diseases, Batten's disease, Tay Sachs, and diabetes. Participants may be grouped as active caregivers or bereaved caregivers who have lost their care recipient. Over one year, and possibly up to five years, participants will complete online surveys about their health, caregiving experiences, and social support networks. They will also take part in two-part phone interviews about their caregiving and social connections. Some may keep a diary every three months to record daily social activities, stress, and feelings. Blood samples may be collected annually for biological analysis. During the study, participants will provide information through surveys, interviews, and diaries, with some giving yearly blood samples. Researchers will assess changes in social, psychological, behavioral, and biological factors related to caregiving. The primary outcome is to track the natural history of caregiver stress over time. Participation involves various tasks and assessments done online or by phone, with follow-ups possible for up to five years to understand long-term effects.