Renal Metabolism of Glycolate to Oxalate

The University of Alabama at Birmingham

Status: Active, not recruiting

Conditions: Healthy

Treatments: Other: Bolus intravenous infusion of 13C2-Glycolate; Other: Oral bolus administration of 13C2-Glycolate; Other: Primed, continuous intravenous infusion of 13C2-Glycolate; Dietary Supplement: Low oxalate controlled Diet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04437225

IRB160505004-GLI

K01DK114332 (U.S. NIH Grant/Contract)

UAB (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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15 participants in 3 patient groups

Constant Infusion of 13C2-Glycolate

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Low oxalate controlled Diet

Other: Primed, continuous intravenous infusion of 13C2-Glycolate

Single Intravenous Dose of 13C2-Glycolate

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Low oxalate controlled Diet

Other: Bolus intravenous infusion of 13C2-Glycolate

Single Oral Dose of 13C2-Glycolate

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Low oxalate controlled Diet

Other: Oral bolus administration of 13C2-Glycolate