Renal Metabolism of Glycolate to Oxalate

Healthy Clinical Trial

Official title:

Renal Metabolism of Glycolate to Oxalate

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04437225
• Other study ID #: IRB-160505004
• Status: Recruiting
• Phase: N/A
• Start date: March 12, 2020
• Est. completion date: December 1, 2025

Study information

• Verified date: May 2024
• Source: University of Alabama at Birmingham
• Contact: Sonia Fargue, M.D., Ph.D.
• Phone: 205-975-6932
• Email: kidneystone[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• Low 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.

Other:
• Primed, 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.
• Bolus 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.
• Oral bolus administration of 13C2-Glycolate
Participants will orally ingest a single dose of carbon-13 glycolate, a naturally occurring form of glycolate.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary oxalate measured by ion chromatography coupled with mass spectrometry	Measurement of carbon 13 labeled and unlabeled urinary oxalate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.	day 5 of dietary control
Primary	Plasma glycolate measured by ion chromatography coupled with mass spectrometry	Measurement of carbon 13 labeled and unlabeled plasma glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.	day 5 of dietary control
Secondary	Urinary creatinine	Baseline assessment of 24hr urinary creatinine under controlled low-oxalate diet.	day 5 of dietary control
Secondary	Urinary glycolate measured by ion chromatography coupled with mass spectrometry	Measurement of carbon 13 labeled and unlabeled urinary glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.	day 5 of dietary control