Clinical trial NCT04603898: Oxalate Formation From Ascorbic Acid
Official title: Oxalate Formation From Ascorbic Acid
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Stone
Keywords: Oxalate
Calcium oxalate stones
Ascorbic Acid
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2020-10-27
Enrollment: 136
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Percent contribution of ascorbic acid (AA) to urinary oxalate excretion
timeFrame: Day 4
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: John Knight, PhD
role: PRINCIPAL_INVESTIGATOR
References: