Oxalate Formation From Ascorbic Acid

• ClinicalTrials.gov Identifier: NCT04603898
• Recruitment Status: Recruiting
• First Posted: October 27, 2020
• Last Update Posted: February 21, 2022
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): John Knight, University of Alabama at Birmingham

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Kidney Stone	Dietary Supplement: Low Oxalate Diet; Dietary Supplement: Carbon-13 Ascorbic Acid Oral Load	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 136 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Oxalate Formation From Ascorbic Acid
• Actual Study Start Date: November 15, 2021
• Estimated Primary Completion Date: December 1, 2024
• Estimated Study Completion Date: February 1, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Body Mass Index (BMI) < 25 or ≥ 30
• 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:

• Tobacco use
• 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

Contacts and Locations

Contacts

Contact: Demond Wiley; 2059343671; kidneystone@uabmc.edu

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35243-3353

Contact: Demond Wiley 205-934-3671 kidneystone@uabmc.edu

Principal Investigator: John Knight

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

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

More Information

• Responsible Party: John Knight, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT04603898
• Other Study ID Numbers: IRB-300005614
• First Posted: October 27, 2020
• Last Update Posted: February 21, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by John Knight, University of Alabama at Birmingham:

Oxalate; Calcium oxalate stones; Ascorbic Acid

Additional relevant MeSH terms:

Kidney Calculi; Nephrolithiasis; Kidney Diseases; Urologic Diseases; Urolithiasis; Urinary Calculi; Calculi; Pathological Conditions, Anatomical; Ascorbic Acid; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Vitamins; Micronutrients