Oxalate Formation From Ascorbic Acid

January 3, 2024 updated by: John Knight, University of Alabama at Birmingham
The purpose of this basic research study is to determine the contribution of endogenous ascorbic acid (AA) turnover to urinary oxalate excretion in both normal BMI and obese adult non-stone formers and calcium oxalate stone formers. The studies proposed will use diets of known nutrient composition, a stable isotope of ascorbic acid (13C6-AA) and mass spectrometric techniques to quantify ascorbic acid turnover to oxalate.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this basic research study is to determine the contribution of endogenous ascorbic acid (AA)turnover to urinary oxalate excretion in both normal BMI and obese adult non-stone formers and calcium oxalate stone formers. The studies proposed will use diets of known nutrient composition, a stable isotope of AA, 13C6-AA, and mass spectrometric techniques to quantify AA turnover to oxalate.

Adults (≥19 years) with and without a history of calcium oxalate kidney stone disease will be recruited from within the greater Birmingham area, and divided into normal BMI (BMI<25 kg/m2) and obese (BMI≥30 kg/m2) groups. Following consent, subjects will meet with a dietitian to ensure willingness to consume controlled diets, and provide fasted blood and 2 x 24 hour urine specimens to determine general health status and adequacy of 24-hour urine collections, respectively.

Eligible subjects will consume a low oxalate controlled diet for 6 days, which will involve 2 days of dietary equilibration followed by oral ingestion of 1 mg/kg carbon-13 AA with breakfast on day 3 and subsequent collection of 4 consecutive 24-hour urine specimens. After the carbon-13 AA load, subjects will return each morning to the Clinical Research Unit for a fasted blood draw, to drop off their 24-hour urine collection, and receive their prepared food. In addition, on day 4, 24 hours after ingesting carbon-13 AA, subjects will collect hourly urine and 1/2 hourly blood samples for 5 hours in the Clinical Research Unit.

Study Type

Interventional

Enrollment (Estimated)

136

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35243-3353
        • Recruiting
        • University of Alabama at Birmingham
        • Principal Investigator:
          • John Knight
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Able to provide informed consent
  • For stone formers: composition of most recent stone > 50% calcium oxalate, no uric acid component
  • For stone formers: first time or recurrent calcium oxalate stone former with stone event within the prior 3 years
  • Two 24-hour urine collections with urinary 24-hour creatinine excretion within 20% of appropriate ratio of creatinine (mg) / body weigh (kg) for gender
  • Willingness to stop supplements (vitamins, Calcium (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, probiotics) for 2 weeks before start and during study
  • Willingness to not undertake vigorous exercise during the study
  • Normal fasting blood Comprehensive Metabolic Panel (CMP)
  • Willingness to ingest menus prepared in Clinical Research Unit at University of Alabama at Birmingham
  • No food allergies or intolerance to any of the foods in study menus
  • If on medications for stone prevention (e.g. thiazides, citrate supplementation excluding calcium citrate), they should have been on a stable dose regimen for at least 8 weeks prior to and during screening, with no changes in dosing anticipated during study protocol. If on allopurinol for stone prevention, stop it for 2 weeks prior to screening and this will not be administered during the study as it has anti-oxidant properties.

Exclusion Criteria:

  • Diabetes
  • Gout
  • Hypertension
  • Estimated Glomerular Filtration Rate (eGFR) less than 60ml/min/1.73m2
  • Primary hyperoxaluria
  • Nephrotic syndrome
  • Enteric hyperoxaluria
  • Renal tubular acidosis
  • Primary hyperparathyroidism
  • Liver disease
  • Auto-immune disorder
  • Neurogenic bladder
  • Urinary diversion
  • Bariatric surgery
  • Active malignancy or treatment for malignancy within 12 months prior to screening
  • Pregnancy
  • Breastfeeding/nursing individuals
  • Females of child bearing age who are not able to use an effective method of birth control during the study
  • Mental/medical condition that is likely to impede successful study completion
  • Illness including flu/common cold/fever 14 days before study and during study
  • Diarrhea or other abnormal gastrointestinal event (e.g. abnormal bowel movements) 14 days before study or during study
  • Abnormal fasting CMP

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Controlled Dietary Study
Subjects will consume a controlled diet (low in oxalate and ascorbic acid) for six days. After two days of equilibration, subjects will provide a blood sample and ingest an oral load of ascorbic acid (1 mg/kg) with breakfast on Day 3. The following day (Day 4), serial blood and urine collections will occur. On Days 5 through 7, subjects will complete a 24-hr urine collection and blood draw.
Dietary supplement: Low Oxalate Diet
Subjects will be instructed to ingest a controlled diet low in oxalate for a total of 4 days
Dietary supplement: Carbon-13 Ascorbic Acid Oral Load
Subjects will be instructed to ingest 1mg/kg of carbon-13 ascorbic acid at breakfast, 2 days after initiating the low oxalate controlled diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent contribution of ascorbic acid (AA) to urinary oxalate excretion
Time Frame: Day 4
On the last day (Day 4) of controlled diet and 24 hours following ingestion of an oral load of carbon-13 AA (1mg/kg), urine and blood will be collected and the levels of carbon 12 and carbon 13 AA and oxalate measured to determine the percent contribution of AA metabolism to urinary oxalate excretion for each subject.
Day 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Investigators

  • Principal Investigator: John Knight, PhD, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2021

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

October 21, 2020

First Submitted That Met QC Criteria

October 21, 2020

First Posted (Actual)

October 27, 2020

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 3, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-300005614

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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