Primary Hyperoxaluria

Researchers are evaluating the safety and tolerability of YOLT-203 in Chinese patients with Primary Hyperoxaluria Type 1 (PH1). This early phase 1 trial also aims to preliminarily assess the effect of a single dose of YOLT-203 on plasma oxalate levels. The study includes a dose-escalation and dose-expansion design with detailed safety and pharmacokinetic assessments. Participants receive a single intravenous dose of YOLT-203 on Day 1 after a screening period of up to 60 days. In the dose-escalation phase, safety, pharmacokinetic, and pharmacodynamic data are reviewed before deciding if a second dose will be given at an effective dose level. After the main study, subjects enter a long-term follow-up period lasting up to 15 years to monitor ongoing safety and outcomes. Participants will be closely monitored with safety assessments through week 52, including blood tests to measure drug levels and effects over time. Pharmacodynamics and pharmacokinetics are evaluated up to day 28 and week 52 respectively. The study collects detailed data on tolerability, plasma oxalate changes, and long-term safety to understand the treatment's impact and risks. The total participation includes screening, treatment, follow-up, and long-term monitoring phases.

Researchers are studying idiopathic calcium oxalate kidney stone disease to understand if patients produce more oxalate within their bodies, leading to higher urinary oxalate levels. The study compares adults with a history of calcium oxalate kidney stones to healthy volunteers without stones. This research aims to evaluate oxalate production and the role of vitamin C and glycolate metabolism in these patients using controlled diets and oral dosing tests. Participants will follow a low-oxalate fixed diet (under 60 mg/day) with normal calcium intake for 5 days. They will then take oral doses of 13C-glycolate and 13C-ascorbic acid on separate visits while continuing the diet. Urine, blood, stool, and breath samples will be collected during these dosing tests over several hours. The study includes screening, dietary equilibration, and oral dosing phases. During the study, participants will collect 24-hour urine samples at home and provide blood and breath samples in the research unit. Researchers will monitor urinary oxalate excretion, endogenous oxalate production, and the contribution of vitamin C breakdown to oxalate levels. The total participation involves multiple visits with dietary control, sample collections, and metabolic tests to assess oxalate synthesis and metabolism.

Researchers are evaluating a genetic newborn screening program for two rare inherited diseases, cystinosis and primary hyperoxaluria (PH), in Germany. These diseases are not detected by routine newborn screening methods but have known common genetic mutations. The study aims to determine if including cystinosis and PH in the general newborn screening should be recommended by comparing early diagnosed infants to those diagnosed later by symptoms, assessing whether early diagnosis and treatment improve outcomes. The study tests newborns using the same dried blood spot card collected for routine newborn screening to detect specific common mutations in the genes associated with cystinosis and PH. If two mutations are found for cystinosis, parents are immediately informed and further diagnostics are arranged. For PH, if one mutation is detected, parents are asked to provide urine samples for additional testing. The study plans to screen 200,000 newborns by 2025, with possible program expansion based on results. Parents who consent allow molecular genetic testing and data sharing for follow-up. Confirmatory tests and clinical care referrals are organized for newborns with positive screening results. Researchers will track the number of newborns diagnosed with cystinosis and PH and those carrying heterozygous mutations. The study includes monitoring for up to 12 months and evaluates whether early detection leads to better health outcomes compared to traditional diagnosis methods.

Researchers are investigating the gut-kidney connection in people with enteric hyperoxaluria, a condition linked to kidney stones and related to inflammatory bowel disease (IBD) or Roux-en-Y gastric bypass (RYGB) surgery. The study will compare 40 participants with these conditions to 40 healthy controls to understand how the gut microbiome affects urinary oxalate levels. This prospective clinical study is sponsored by NYU Langone Health and focuses on how diet influences oxalate metabolism in these groups. Participants will follow a controlled diet with moderately high oxalate content for specific periods (Days 0-3 and 21-24) and consume sodium oxalate via prepared spinach from Days 8-20. There is a washout period on Days 4-7 where participants eat ad-lib diets supplemented with daily spinach. The diets are carefully controlled for protein, fat, carbohydrate, calcium, oxalate, ascorbic acid, and fiber. During the study, hydration is maintained by providing bottled water daily. Participants will provide multiple biological samples including four stool collections, four 24-hour urine collections, and two blood samples. Colonic permeability will also be tested four times. The main measurements are urinary oxalate levels on Days 2-3 and 23-24. Additional measurements include fecal oxalate, urinary calcium, sucralose, calcium oxalate supersaturation, and plasma oxalate levels at various time points. The study will help clarify the impact of diet and microbiome on oxalate metabolism over the study period.

Researchers are evaluating whether patients with idiopathic calcium oxalate kidney stones absorb more dietary oxalate, which may cause increased oxalate in their urine. The study includes adults with a history of calcium oxalate kidney stones and healthy volunteers without stones. The aim is to understand oxalate absorption using diets with different oxalate levels and a soluble oxalate test. Participants will follow fixed diets: a low-oxalate diet (under 60 mg/day) and a moderately high-oxalate diet (250-300 mg/day), each with normal calcium levels. They will complete a soluble oxalate gut absorption test by ingesting labeled oxalate and sucralose. The study involves three phases: screening and low-oxalate diet with urine collection; a 13C2-oxalate absorption test with blood, urine, breath, and stool samples; and a high-oxalate diet phase with urine and blood testing. During the study, participants will provide multiple samples including urine, blood, stool, and breath to measure oxalate absorption and synthesis. They will keep fixed diets for several days and collect urine at home. Researchers will monitor urinary oxalate excretion and absorption of soluble oxalate. The total participation includes diet periods, tests, and sample collections lasting over several weeks, with safety monitoring and wash-out periods between diets.

This research aims to evaluate a drug called lumasiran in patients with kidney disease who require haemodialysis and have high levels of oxalate in their blood. People with kidney disease often face higher risks of heart attacks, heart disease, and strokes, possibly linked to elevated oxalate levels. The study will investigate whether lumasiran can reduce oxalate levels in these patients and monitor any changes in their heart health using echocardiograms. Participants will be randomly assigned to receive either lumasiran or a placebo, both given as subcutaneous injections with three monthly loading doses followed by one maintenance dose. The study is double-blind, meaning neither the participants nor the doctors will know which treatment is given until the study concludes. Monthly blood tests will measure pre-dialysis plasma oxalate levels, and echocardiograms will be performed at the start and after six months. During the study, participants will attend monthly visits for blood tests alongside their dialysis sessions, and heart ultrasounds will be done at baseline and six months to assess cardiac changes. Researchers will monitor oxalate levels, side effects, inflammatory and cardiovascular biomarkers, and overall tolerability of lumasiran. The study duration is six months, with data collected regularly to evaluate the drug's impact on oxalate reduction and heart health.

Researchers are studying monogenic kidney stone diseases to identify the specific genes and genetic changes that cause these conditions. The study aims to understand the features of kidney stone disease linked to particular genes and mutations. This knowledge may help in developing better treatments for these rare kidney stone diseases. Participants will provide a blood sample or buccal cell sample for DNA or RNA testing and complete a kidney stone history questionnaire. Family members may also be asked to provide a 24-hour urine collection for additional analysis. Genetic testing will be conducted on these samples, and results will be shared with the participant's local doctor. Samples will be stored for future research, but family members of patients without known mutations will not be tested. During the study, participants provide medical and family history information and biological samples for genetic testing. Researchers will evaluate the symptomatic onset of monogenic stone disease over five years and study genotype markers. Participation involves providing samples and questionnaires, with follow-up over time to better understand the disease. The study is observational, focusing on collecting data rather than testing treatments.

Researchers are collecting information from patients with rare kidney diseases to support research and improve care. This National Registry of Rare Kidney Diseases (RaDaR) aims to develop clinical guidelines, audit treatments and outcomes, and help develop future therapies by gathering comprehensive data. Rare kidney diseases often have genetic causes and affect patients from childhood into adulthood, but their rarity makes research and treatment development challenging. The registry gathers clinical data and biological samples from various rare kidney disease groups, each focusing on conditions like Alport Syndrome, APRT Deficiency, Polycystic Kidney Disease, and many others. It connects patients and clinicians and allows patients to contribute information about their quality of life. This infrastructure enables identification of patient groups for clinical trials, biomarker development, and genotype-phenotype studies. Participants provide clinical and disease-specific information over time, which supports epidemiological and translational research. The registry facilitates patient recruitment for studies, improves patient and clinician education, and provides access to current knowledge about rare kidney diseases. The registry is ongoing and primarily includes UK patients but also accepts international participants consented through UK NHS hospitals.

Researchers are investigating whether colonization with the gut bacteria Oxalobacter formigenes can reduce urinary oxalate levels in adults with a history of calcium oxalate kidney stones who are not currently colonized with this bacteria. The study aims to better understand how this bacterial colonization affects oxalate excretion and kidney stone formation. Participants will follow fixed diets with controlled amounts of oxalate to assess these effects. The study includes several phases: screening and pre-colonization, colonization and post-colonization, and a follow-up phase. During pre-colonization, participants consume low and moderately high oxalate diets for 4 days each, collecting urine, blood, and stool samples. After that, they ingest a live preparation of Oxalobacter formigenes to induce colonization, which is confirmed by stool testing. Post-colonization, participants repeat the same diet and sample collection process. Follow-up visits occur every 6 months for up to 4 years to monitor colonization sustainability and collect additional samples. Throughout the study, participants provide multiple 24-hour urine collections, blood samples, and stool samples to measure urinary oxalate and confirm bacterial colonization. Researchers will evaluate changes in urinary oxalate excretion two months after colonization and the long-term maintenance of colonization over four years. Participants are also monitored for diet adherence and complete questionnaires during follow-up visits. The total study duration includes initial diet phases, colonization, and several years of follow-up assessments.

Researchers are evaluating ABO-101 to study its safety, tolerability, how the body processes it, and its effects in people with primary hyperoxaluria type 1 (PH1), a rare genetic condition. This Phase 1/2 clinical trial aims to find a recommended dose for adults and then assess this dose in children. The study is sponsored by Arbor Biotechnologies and includes a long-term follow-up to meet regulatory requirements. The trial has two main study periods. In the first period, Part A involves adults receiving single increasing doses of ABO-101 through an intravenous infusion to identify a suitable dose. Part B then treats pediatric participants with the chosen dose. After these parts, the second study period begins, focusing on long-term monitoring for safety and treatment effects. Participants will have regular assessments including monitoring for any treatment-related side effects over six months, measuring changes in urine oxalate and plasma glycolate levels, and tracking kidney function for up to two years. Blood and urine samples will be collected to study drug components and immune responses. The trial involves careful safety follow-up and ongoing evaluation throughout the study duration.