Oxalate Formation From Ascorbic Acid
Primary Purpose
Kidney Stone
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low Oxalate Diet
Carbon-13 Ascorbic Acid Oral Load
Sponsored by
About this trial
This is an interventional basic science trial for Kidney Stone focused on measuring Oxalate, Calcium oxalate stones, Ascorbic Acid
Eligibility Criteria
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
Sites / Locations
- University of Alabama at BirminghamRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Controlled Dietary Study
Arm Description
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.
Outcomes
Primary Outcome Measures
Percent contribution of ascorbic acid (AA) to urinary oxalate excretion
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04603898
First Posted
October 21, 2020
Last Updated
November 15, 2022
Sponsor
University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT04603898
Brief Title
Oxalate Formation From Ascorbic Acid
Official Title
Oxalate Formation From Ascorbic Acid
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2021 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Stone
Keywords
Oxalate, Calcium oxalate stones, Ascorbic Acid
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
136 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Controlled Dietary Study
Arm Type
Experimental
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Low Oxalate Diet
Intervention Description
Subjects will be instructed to ingest a controlled diet low in oxalate for a total of 4 days
Intervention Type
Dietary Supplement
Intervention Name(s)
Carbon-13 Ascorbic Acid Oral Load
Intervention Description
Subjects will be instructed to ingest 1mg/kg of carbon-13 ascorbic acid at breakfast, 2 days after initiating the low oxalate controlled diet.
Primary Outcome Measure Information:
Title
Percent contribution of ascorbic acid (AA) to urinary oxalate excretion
Description
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.
Time Frame
Day 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Demond Wiley
Phone
2059343671
Email
kidneystone@uabmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Knight, PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35243-3353
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Demond Wiley
Phone
205-934-3671
Email
kidneystone@uabmc.edu
First Name & Middle Initial & Last Name & Degree
John Knight
12. IPD Sharing Statement
Plan to Share IPD
No
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Oxalate Formation From Ascorbic Acid
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