Amino Acid Metabolism 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 conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore its possible links with various underlying diseases. This non-interventional, multicenter study aims to provide a pilot map of genetic variation in HLA that may be useful in medical research and clinical applications related to selected diseases. The study plans to include 12,000 participants over a total duration of 36 months. Each participant will attend one visit at a participating site during which they will provide demographic data, lifestyle information such as smoking and alcohol use, blood pressure measurements, details on diagnosed diseases and treatments, and recent laboratory test results if available. Buccal swab samples will be collected from each participant to extract DNA for HLA genotyping analysis. Selected samples will undergo further whole genome sequencing to investigate associations with autoimmune diseases. Participants will receive a personalized ancestry report after analysis completion. During the study visit, data collection includes demographic and health information, as well as laboratory and clinical test results from the past year. The genetic material from buccal swabs will be stored and processed for genetic analysis. Researchers will measure allele frequency of HLA alleles in the Greek population and assess the prevalence and risk associations of selected HLA-related diseases. The study's total duration is 36 months with results available at the end of this 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.

This research aims to observe the effects of Palynziq (pegvaliase) treatment in pregnant women with phenylketonuria (PKU) and on their babies exposed to pegvaliase during pregnancy and breastfeeding. The study is a Phase 4 observational trial that evaluates maternal, fetal, and infant outcomes related to pegvaliase exposure. It includes women diagnosed with PKU who were treated with pegvaliase from two weeks before their last menstrual period (LMP) or at any time during pregnancy. Participants are pregnant women prescribed pegvaliase by their healthcare provider who enroll through a centralized call center. The study collects data retrospectively from at least three months before the LMP, through pregnancy, and during the infant's first year of life. The timing and duration of pegvaliase exposure during pregnancy and breastfeeding, including each trimester, are recorded. Individual participation lasts up to about 21 months. During the study, information will be gathered from the participant's healthcare providers and the infant's doctors. Researchers will monitor pregnancy outcomes and infant development over ten years, focusing on pegvaliase exposure effects. The study also tracks serious adverse events and pegvaliase use during breastfeeding. This long-term monitoring aims to provide detailed data on maternal and infant health following pegvaliase exposure.

Researchers are conducting a 10-year multi-center, prospective, longitudinal study in the United States to observe immunologic, inflammatory, and laboratory changes in people with phenylketonuria (PKU) who are treated with Palynziq (pegvaliase). The study includes both new users starting pegvaliase within 30 days after enrolling in a related study (165-501) and those who have already been receiving the treatment before enrollment. The goal is to understand long-term immune and inflammatory responses to this treatment. Participants must already be enrolled in the 165-501 study to join this study. They will provide blood samples before dosing every three months for the first three years, then every six months for the remaining study period. Additional blood samples may be taken during safety events as defined in the related 165-501 study protocol, and standard care blood draws are also incorporated. Blood tests will measure phenylalanine levels and various immune and inflammatory markers, which will be processed centrally. During the study, data from this observational study will be combined with data from the 165-501 study to reduce duplicate reporting and lessen the burden on study sites. Participants may withdraw from this study while continuing in the 165-501 study, but not vice versa, to ensure safety monitoring. The research team will evaluate immune and inflammatory responses over up to 10 years of treatment, tracking changes through blood tests and clinical data collection for a comprehensive understanding of long-term effects.

Researchers are evaluating the long-term safety of JNT-517 in children and adults with Phenylketonuria (PKU), a condition caused by a deficiency in the PAH enzyme. This Phase 3, open-label study includes participants who completed previous JNT-517 studies as well as those new to JNT-517 treatment. The goal is to understand how the drug performs over an extended period when used consistently in this population. All participants will receive JNT-517 orally twice daily with doses adjusted for age and weight. The study will follow a fixed dosing schedule regardless of prior exposure to JNT-517. Participants will be monitored for treatment-emergent adverse events and changes in blood and urine phenylalanine levels, dietary intake, and attention-related symptoms among children previously treated. Participants will attend regular visits for safety assessments, blood tests, dietary evaluations, and symptom rating scales. Plasma drug concentrations will be measured at specific times in younger children to understand drug levels. The study tracks adverse events from screening through two weeks after the last dose. Total participation duration may last up to approximately five years, allowing long-term safety and efficacy monitoring.

Researchers are conducting a 10-year global, multi-center observational study to better understand the safety profile of pegvaliase, a treatment for Phenylketonuria (PKU). The study focuses on monitoring hypersensitivity reactions, long-term safety, tolerability, and the effectiveness of risk minimization measures used in the European Union. Both new users starting pegvaliase within 30 days of enrollment and those who have already been receiving pegvaliase can participate. Participants in this study will not receive any experimental treatments or undergo special procedures as part of the trial. Instead, their usual pegvaliase treatment and clinical care will continue as normal. Information about their medical history, pegvaliase use, other medications, and safety concerns such as allergic reactions and injection site issues will be collected by their primary physicians. Safety events will be reviewed periodically by an independent committee. Participants are followed according to routine clinical practice, with clinical outcomes assessed regularly, typically monthly during initial treatment phases and every six months during maintenance. The study measures risks of specific safety events over up to 10 years of pegvaliase treatment in a real-world setting. There are no mandatory study visits, and all data collection is based on regular medical care visits.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and effectiveness of an investigational drug called GNR-055 in patients with Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome. This condition is a genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase (ID2S), leading to harmful buildup of certain substances in cells that affects growth, organs, and the nervous system. The study is a phase 2/3, multicenter, open-label trial involving different age groups to better understand how GNR-055 works and its safety profile. GNR-055 is a modified enzyme replacement therapy designed to cross the blood-brain barrier, potentially preventing neurological damage and improving quality of life for patients with MPS II. Participants receive weekly intravenous infusions of GNR-055 at doses ranging from 1.0 to 3.0 mg/kg, depending on their study group. The study includes multiple cohorts, with adult and pediatric patients receiving specific dosing regimens over the trial period. During the study, participants will undergo various assessments including monitoring of adverse events, urine and serum levels of glycosaminoglycans (GAG), cerebrospinal fluid analysis, joint motion measurements, MRI scans of liver, spleen, and brain, heart and lung function tests, neurocognitive evaluations, and biomarker analysis. These evaluations occur at baseline and multiple follow-up visits up to week 56. The study aims to gather detailed data on the drug's impact on disease symptoms, safety, and biological markers to inform future treatment options.

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 pyrimidine and purine metabolism disorders (DPPMs), which affect how the body processes certain chemicals and can cause a range of symptoms from mild to severe, impacting the brain, blood, kidneys, and immune system. This research aims to better understand the causes, features, and outcomes of these disorders by comparing affected individuals, their unaffected family members, and healthy volunteers. The study focuses on both known and novel DPPMs and seeks to identify genomic, clinical, pharmacological, laboratory, and dietary factors influencing disease variability. Participants are divided into three groups: those diagnosed with DPPMs, their family members without the disorder, and healthy volunteers. Affected participants visit the clinic at least once a year, undergoing physical exams, sample collections (blood, urine, saliva, stool), and various tests depending on symptoms, which may include skin and mouth swabs, heart, kidney, brain, and nerve function tests, dental, hearing, and vision exams, learning assessments, physical activity monitoring, imaging scans, and photographs. These evaluations may be spread over up to seven days, and affected participants may remain in the study indefinitely. Family members and healthy volunteers have a single study visit with a physical exam and sample collections. Throughout the study, researchers collect DNA and biological samples for genetic, biochemical, enzyme, and microbiome analyses. The study includes detailed clinical and laboratory assessments to track disease features and variability. Participants' medical, laboratory, and imaging data are collected following standard care protocols. The primary outcome is to describe features of poorly characterized DPPMs, while secondary outcomes focus on identifying factors associated with different clinical results. The study involves long-term monitoring and may continue indefinitely for affected individuals.