Assessment of Endogenous Oxalate Synthesis

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Recruiting

CT.gov ID

NCT05229952

Collaborator

(none)

Enrollment

Location

Arm

103.7

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to determine the daily rate of endogenous synthesis of oxalate using carbon 13 oxalate isotope tracer technique and a low-oxalate controlled diet.

Condition or Disease	Intervention/Treatment	Phase
Healthy Kidney Stone Obesity	Dietary Supplement: Low-oxalate controlled diet Other: Primed, continuous intravenous infusion of 13C2-oxalate	N/A

Detailed Description

Urinary oxalate excretion is derived from both dietary sources and endogenous synthesis. This study will use low-oxalate controlled diet and intravenous infusion of the isotope tracer carbon 13 oxalate, timed with blood and urine collections, to determine the daily rate of endogenous oxalate synthesis in non-stone forming volunteers and in subjects with calcium oxalate kidney stones. A DXA scan will be used to assess body composition.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Assessment of Endogenous Oxalate Synthesis

Actual Study Start Date :

Feb 10, 2022

Anticipated Primary Completion Date :

Oct 1, 2029

Anticipated Study Completion Date :

Oct 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Constant infusion of 13C2-oxalate Subjects who have passed screening, will consume a low-oxalate, normal calcium controlled diet for 5 days total. On Days 3 and 4, subjects will collect two 24-hour urines. On Day 5, they will receive a carbon 13 oxalate infusion which will occur at a constant rate for 6 hours, in the fasted state, following a priming dose. Hourly urine and twice hourly blood samples will be collected during the 6 hours. Meals will be resumed at the end of the infusion and timed urine collections will take place at home until the next day. A DXA scan will be performed to assess body composition at another date.	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 for 5 days. 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-oxalate Participants will receive a continuous intravenous administration of carbon-13 oxalate, a naturally occurring form of oxalate, over the course of several hours until steady-state is achieved, using an IV catheter, while remaining fasting.

Arm

Intervention/Treatment

Experimental: Constant infusion of 13C2-oxalate

Subjects who have passed screening, will consume a low-oxalate, normal calcium controlled diet for 5 days total. On Days 3 and 4, subjects will collect two 24-hour urines. On Day 5, they will receive a carbon 13 oxalate infusion which will occur at a constant rate for 6 hours, in the fasted state, following a priming dose. Hourly urine and twice hourly blood samples will be collected during the 6 hours. Meals will be resumed at the end of the infusion and timed urine collections will take place at home until the next day. A DXA scan will be performed to assess body composition at another date.

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 for 5 days. 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-oxalate

Participants will receive a continuous intravenous administration of carbon-13 oxalate, a naturally occurring form of oxalate, over the course of several hours until steady-state is achieved, using an IV catheter, while remaining fasting.

Outcome Measures

Primary Outcome Measures

Endogenous Oxalate Synthesis Rate [day 5]
Daily oxalate synthesis rate (mg/day) determined by the 13c2-oxalate infusion method

Secondary Outcome Measures

Urinary Oxalate excretion [day 3-4]
24-hr urinary oxalate excretion (mg/day) after equilibration on the low-oxalate controlled diet, measured by ion chromatography coupled with mass spectrometry.
Urinary creatinine excretion [day 3-4]
24-hr urinary creatinine excretion (g/day) after equilibration on the low-oxalate controlled diet.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Mentally competent adults, able to read and comprehend the consent form
Body Mass Index (BMI) between 18.5 and 45 kg/m2
Acceptable 24 hour urine collections (judged on screening)
for non-stone formers, good health as judged from a medical history, reported medications, and a complete blood metabolic profile, baseline urinary oxalate excretion < 40 mg/day
for kidney stone formers: first time or recurrent CaOx stone former with stone event within the prior 3 years. Composition of most recent stone (if known) > 50% calcium oxalate, without uric acid component.

Exclusion Criteria:

History of any hepatic, bowel, or endocrine disease or 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 years
BMI <18.5 or >45 kg/m2