Healthy, Healthy Volunteer, Kidney Calculi, Kidney Stones, Nephrolithiasis, Nephrolithiasis, Calcium Oxalate, Oxalate Urolithiasis, Urolithiasis, Urolithiasis, Calcium Oxalate
Conditions
Keywords
oxalate synthesis
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.
Interventions
DIETARY_SUPPLEMENTLow-oxalate diet and glycolate dosing
Low-oxalate diet 4 days of fixed eucaloric diet with low oxalate (\<60 mg/day), normal calcium content (600-1000 mg/day)
DIETARY_SUPPLEMENTOral glycolate dosing
Oral 13C-glycolate dosing (0.5 mg/kg)
DIETARY_SUPPLEMENTOral 13C- ascorbic acid dosing
Oral 13C- ascorbic acid dosing (0.75 mg/kg)
Sponsors
University of Alabama at Birmingham
University of Texas, Southwestern Medical Center at Dallas
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated endogenous oxalate synthesis (oxalate mg/day) | 1 day | Basal rate of endogenous oxalate synthesis estimated by repeat fasted hourly urine collections (mg/day) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour urinary oxalate excretion on low oxalate diet | 2 days | mean 24-hour urinary oxalate excretion on the low oxalate diet (mg/day) |
| contribution of ascorbic acid breakdown to urinary oxalate excretion | 2 days | contribution of ascorbic acid breakdown to oxalate synthesis (%) |
Countries
United States
Contacts
CONTACTSonia Fargue, PhD
PRINCIPAL_INVESTIGATORSonia Fargue, PhD
University of Alabama at Birmingham
Outcome results
None listed