Oxalate Formation From Ascorbic Acid

NCT ID: NCT04603898

Last Updated: 2026-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-15

Study Completion Date

2026-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Kidney Stone

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Low Oxalate Diet

Intervention Type DIETARY_SUPPLEMENT

Subjects will be instructed to ingest a controlled diet low in oxalate for a total of 4 days

Carbon-13 Ascorbic Acid Oral Load

Intervention Type DIETARY_SUPPLEMENT

Subjects will be instructed to ingest 1mg/kg of carbon-13 ascorbic acid at breakfast, 2 days after initiating the low oxalate controlled diet.

Interventions

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Low Oxalate Diet

Subjects will be instructed to ingest a controlled diet low in oxalate for a total of 4 days

Intervention Type 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.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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John Knight

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John Knight, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Demond Wiley

Role: CONTACT

2059343671

Facility Contacts

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Demond Wiley

Role: primary

205-934-3671

Other Identifiers

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R01DK126774

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-300005614

Identifier Type: -

Identifier Source: org_study_id

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