Clinical trial NCT06989320: Endogenous Oxalate Synthesis in Idiopathic Calcium Oxalate Kidney Stone Disease
Official title: Endogenous Oxalate Synthesis in Idiopathic Calcium Oxalate Kidney Stone Formers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Stones
Kidney Calculi
Urolithiasis
Urolithiasis, Calcium Oxalate
Nephrolithiasis
Nephrolithiasis, Calcium Oxalate
Oxalate Urolithiasis
Healthy
Healthy Volunteer
Keywords: oxalate synthesis
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: University of Texas, Southwestern Medical Center at Dallas
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2025-05-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial study is to test if patients with idiopathic calcium oxalate kidney stones have an increased production of oxalate by the body, which would lead to increased urinary excretion of oxalate.

The study will recruit adult patients with a history of calcium oxalate kidney stones and healthy volunteers without kidney stones.

Participants will

ingest fixed diets containing low amounts of oxalate for 5 days ingest a soluble form of glycolate and vitamin C collect urine, blood, stool during the dietary and oral dosing portions of the study and also collect breath sample during the oral glycolate test

Detailed description: In this study the investigators propose to measure the production of oxalate by the body (endogenous oxalate synthesis), after equilibration on a low oxalate diet (\<60 mg oxalate/day, 600-800 mg calcium/day) and estimate the importance of vitamin C and glycolate metabolism to oxalate production in both Calcium Oxalate Kidney Stone patients and matched controls by oral dosings of those two substances.

Phase 1. Screening and low-oxalate diet 24-hr urinary excretions. Between the University of Alabama at Birmingham (UAB) and the University of Texas Southwestern Medical Center (UTSW), the study will enroll 40 subjects with idiopathic Calcium Oxalate Kidney Stone (20 Males/20 Females) and 40 non-kidney stone forming controls (20 Males/20 Females). Participants in the two groups will be matched for age (within 10 yrs) and gender. Screening will include blood complete metabolic profile and two 24-hour urine specimens collected at home on self-choice diets and anthropometric measurements.

Participants will then ingest the controlled low-oxalate (\<60 mg/day) diet for 5 consecutive days and collect two 24-hour urines after 2 days of dietary equilibration.

Phase 2. Oxalate production and 13C-glycolate dosing tests. On Day 5, participants will arrive after an overnight fast in the research unit to undergo the oral 13C-glycolate dosing test. After a 1-hour baseline urine collection, they will ingest an oral load containing 0.5 mg/kg body weight of 13C-glycolate, dissolved in bottled water. For the next 7 hours, blood and urine will be collected hourly, and breath as more time points. They will remain on the fixed diet for 24 hours with a meal 7 hours post-load, and dinner at home 12 hours post-load. They will collect the remainder of their 24-hour urine at home.

Phase 3. Oxalate production and 13C-ascorbic acid dosing tests. After 1 day of equilibration on the same low-oxalate diet, participants will arrive after an overnight fast in the research unit to provid eone blood and one urine sample and then ingest an oral dose of 13C-ascorbic acid (0.75 mg/kg), return home and continue to ingest the low-oxalate diet. The next morning, participants will arrive after an overnight fast in the research unit. For the next 7 hours, blood and urine will be collected hourly. They will remain on the fixed diet for 24 hours with a meal at the end of the visit.

Eligibility criteria: Inclusion Criteria:

* age 18-80 yrs
* Body Mass Index \> 18.5 kg/m2
* Normal fasting serum electrolytes on comprehensive metabolic profile
* Willing to ingest fixed diets
* Willing to stop supplements (vitamins including vitamin C, calcium (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, probiotics) for 2 weeks before start and during study.
* For stone formers: first time or recurrent Calcium Oxalate stone former. Composition of most recent stone ≥ 50% calcium oxalate if available, uric acid component \<20%

Exclusion Criteria:

* Chronic Kidney Disease stage 4-5
* Primary hyperoxaluria, Enteric (secondary) hyperoxaluria
* Liver, bowel, endocrine or renal diseases (other than idiopathic Calcium Oxalate kidney stones) or any other condition that may influence the absorption, transport or urinary excretion of ions, which will compromise the interpretation of results, including: Cystic fibrosis, Celiac disease, Cystinuria, Uric acid stone former, Nephrotic syndrome, Sarcoidosis, Renal tubular acidosis, Primary hyperparathyroidism, Neurogenic bladder, Urinary diversion, Chronic diarrhea, Bariatric surgery, Inflammatory bowel disease
* Pregnancy or breast-feeding
* Incompatible dietary requirements with the study, food allergies or intolerance to any of the foods in study menus
* Active malignancy or treatment for malignancy within 12 months prior to screening
* Utilization of immunosuppressive medication
* Uncontrolled hypertension or diabetes
* Diabetes type 1

Primary outcomes:
measure: Estimated endogenous oxalate synthesis (oxalate mg/day)
timeFrame: 1 day
Secondary outcomes:
measure: 24-hour urinary oxalate excretion on low oxalate diet
timeFrame: 2 days
measure: contribution of ascorbic acid breakdown to urinary oxalate excretion
timeFrame: 2 days
Other outcomes:
measure: Contribution of glycolate metabolism to urinary oxalate
timeFrame: 1 day
Locations:
city: Birmingham
country: United States
facility: United States, Alabama University of Alabama at Birmingham
state: Alabama
city: Dallas
country: United States
facility: University of Texas South Western Medical Center
state: Texas
Study officials:
affiliation: University of Alabama at Birmingham
name: Sonia Fargue, PhD
role: PRINCIPAL_INVESTIGATOR
References: