Assessment of Endogenous Oxalate Synthesis

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Obesity; Kidney Stone
• Intervention / Treatment: Dietary supplement: Low-oxalate controlled diet; Other: Primed, continuous intravenous infusion of 13C2-oxalate

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 Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sonia Fargue, PhD; Phone Number: 205-9756932; Email: kidneystone@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Sonia Fargue, PhD; Phone Number: 205-975-6932; Email: kidneystone@uabmc.edu
      • Contact: Research Coordinator; Phone Number: 205-9345712; Email: kidneystone@uabmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Mentally competent adults, able to read and comprehend the consent form
• Body Mass Index (BMI) between 18.5 and 50 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 >50 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous Oxalate Synthesis Rate	Daily oxalate synthesis rate (mg/day) determined by the 13c2-oxalate infusion method	day 5

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Sonia Fargue, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Urolithiasis; Nephrolithiasis; Kidney stones; Oxalate; Urologic disease; Oxalate metabolism
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: IRB-151020005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No