Renal Metabolism of Glycolate to Oxalate
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Urinary oxalate measured by ion chromatography coupled with mass spectrometry
研究概览
简要总结
This study will determine the contribution of glycolate metabolism to urinary oxalate excretion in healthy subjects, using carbon 13 isotope glycolate tracer technique and a low-oxalate controlled diet.
详细描述
It is known that glycolate, an intermediary molecule in normal metabolism, can be converted into oxalate. The origin of urinary oxalate is of interest as calcium oxalate is a main component of kidney stones. In the rare disease primary hyperoxaluria, excessive production of oxalate by the body results in frequent kidney stones and can cause loss of kidney function. Primary hyperoxaluria is caused by deficiencies in one of several enzymes involved in the glycolate pathway.
This study will seek to determine how much oxalate is formed from glycolate in normal subjects. After consuming a controlled diet, subjects will either ingest or have an intravenous infusion of carbon 13 glycolate, a stable isotope of glycolate that can be tracked and will also label downstream metabolic products. Blood and urine samples will be assessed for their amounts of labeled glycolate and labeled oxalate to provide an accurate measure of how much oxalate is made from normal glycolate breakdown in healthy human subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Mentally competent adults, able to read and comprehend the consent form
- •18-75 years of age
- •Body Mass Index (BMI) between 19 and 40
- •In good health as judged from a medical history, reported medications, and a complete blood metabolic profile
- •Acceptable 24 hour urine collections (performed twice for screening)
排除标准
- •History of any hepatic, renal, bowel, or endocrine disease or any other condition that may influence the absorption, transport or urine excretion of ions
- •Abnormal urine chemistries or blood metabolic profiles
- •Poor 24 hour urine collections completed during screening, judged by 24 hour urine creatinine excretion (indicative of not collecting all urine in the 24 hour period)
- •Pregnancy, intention to become pregnant in the near future, or lactation
- •Aged <18 or >75
- •BMI <19 or >40
研究组 & 干预措施
Constant Infusion of 13C2-Glycolate
Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 5:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 7:30 am for the carbon 13 glycolate infusion which will occur at a constant rate for 10 hours, following a priming dose. From 7:30 am to 5:30 pm, urine collections will occur hourly, and from 8:30 am to 5:30 pm, IV blood collections will occur every half hour. Subjects will receive a meal at 5:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
干预措施: Low oxalate controlled Diet (Dietary Supplement)
Constant Infusion of 13C2-Glycolate
Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 5:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 7:30 am for the carbon 13 glycolate infusion which will occur at a constant rate for 10 hours, following a priming dose. From 7:30 am to 5:30 pm, urine collections will occur hourly, and from 8:30 am to 5:30 pm, IV blood collections will occur every half hour. Subjects will receive a meal at 5:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
干预措施: Primed, continuous intravenous infusion of 13C2-Glycolate (Other)
Single Intravenous Dose of 13C2-Glycolate
Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 8:30 am for a single dose of carbon-13 glycolate to be administered. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, IV blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
干预措施: Low oxalate controlled Diet (Dietary Supplement)
Single Intravenous Dose of 13C2-Glycolate
Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 8:30 am for a single dose of carbon-13 glycolate to be administered. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, IV blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
干预措施: Bolus intravenous infusion of 13C2-Glycolate (Other)
Single Oral Dose of 13C2-Glycolate
Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. At 8:30 am, subjects will ingest the carbon-13 glycolate, dissolved in to 50 ml (about 1/4 cup) of water. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, intravenous (IV) blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
干预措施: Low oxalate controlled Diet (Dietary Supplement)
Single Oral Dose of 13C2-Glycolate
Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. At 8:30 am, subjects will ingest the carbon-13 glycolate, dissolved in to 50 ml (about 1/4 cup) of water. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, intravenous (IV) blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
干预措施: Oral bolus administration of 13C2-Glycolate (Other)
结局指标
主要结局
Urinary oxalate measured by ion chromatography coupled with mass spectrometry
时间窗: day 5 of dietary control
Measurement of carbon 13 labeled and unlabeled urinary oxalate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
Plasma glycolate measured by ion chromatography coupled with mass spectrometry
时间窗: day 5 of dietary control
Measurement of carbon 13 labeled and unlabeled plasma glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
次要结局
- Urinary creatinine(day 5 of dietary control)
- Urinary glycolate measured by ion chromatography coupled with mass spectrometry(day 5 of dietary control)
研究者
Sonia Fargue
Principle Investigator
University of Alabama at Birmingham