Healthy
Conditions
Keywords
oxalate metabolism, kidney stones, glycolate, isotope tracer study, urolithiasis, oxalate
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTLow oxalate controlled Diet
Participants will consume a diet that is controlled in its contents of protein, carbohydrates, fat, calcium, oxalate, vitamin C and sodium. Participants will be asked not to take any dietary supplements, exercise strenuously, or consume food or drink that is not provided to them.
OTHERPrimed, continuous intravenous infusion of 13C2-Glycolate
Participants will receive a continuous intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, over the course of several hours until steady-state is achieved, using an IV catheter.
OTHERBolus intravenous infusion of 13C2-Glycolate
Participants will receive a bolus intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, using an IV catheter.
OTHEROral bolus administration of 13C2-Glycolate
Participants will orally ingest a single dose of carbon-13 glycolate, a naturally occurring form of glycolate.
Sponsors
University of Alabama at Birmingham
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Subject will undergo the gold-standard technique of steady-state intravenous infusion of 13-glycolate administration. Selected subjects will also undergo other modified modalities of 13-glycolate administration.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary oxalate measured by ion chromatography coupled with mass spectrometry | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary creatinine | day 5 of dietary control | Baseline assessment of 24hr urinary creatinine under controlled low-oxalate diet. |
| Urinary glycolate measured by ion chromatography coupled with mass spectrometry | day 5 of dietary control | Measurement of carbon 13 labeled and unlabeled urinary glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSonia Fargue, M.D., Ph.D.
University of Alabama at Birmingham
Outcome results
None listed