Kidney Calculi, Kidney Stone, Nephrolithiasis, Nephrolithiasis, Calcium Oxalate, Oxalate Urolithiasis, Oxaluria, Urolithiasis, Urolithiasis, Calcium Oxalate
Conditions
Brief summary
The goal of this trial is to test if colonization with the gut bacteria Oxalobacter formigenes leads to a reduction in urinary oxalate excretion in patients with calcium oxalate kidney stone disease. The study will recruit adult participants with a history of calcium oxalate kidney stones who are not colonized with Oxalobacter formigenes. Participants will * ingest fixed diets containing low and moderately high amounts of oxalate for 4 days at a time * collect urine, blood and stool samples during the fixed diets * ingest a preparation of live Oxalobacter formigenes to induce colonization with Oxalobacter formigenes
Detailed description
In this study the investigators propose to measure the excretion of urinary oxalate on a fixed diet with controlled amounts of oxalate, before and after inducing colonization with the gut bacteria Oxalobacter formigenes in individuals with a history of calcium oxalate kidney stones not already colonized with Oxalobacter formigenes. Screening and Pre-colonization phase. Between the University of Alabama at Birmingham (UAB) and the University of Texas Southwestern Medical Center (UTSW), the study will enroll 40 individuals with a history of idiopathic calcium oxalate kidney (20 males/20 females). Screening will include stool colonization testing, blood complete metabolic profile, 24-hr urine specimens collected at home on self-selected diets and anthropometric measurements. Participants will ingest a low-oxalate (\<60 mg/day) fixed diet for 4 consecutive days and collect two 24-hr urines and a stool sample after 2 days of dietary equilibration, as well as one fasted blood sample on the last morning. After a wash-out period of at least 1 week, participants will ingest a moderately high-oxalate (250-300 mg/day) fixed diet for 4 consecutive days and collect two 24-hr urines and a stool sample after 2 days of dietary equilibration, as well as one fasted blood sample on the last morning. Colonization and Post-colonization phase. Participants will be colonized with Oxalobacter formigenes by ingesting a freshly thawed paste of live bacterial preparation of O. formigenes. They will collect a stool sample 1 week later to assess if colonization occured. After confirmation of successful colonization, participants will ingest a low-oxalate (\<60 mg/day) fixed diet for 4 consecutive days and collect two 24-hr urines and a stool sample after 2 days of dietary equilibration, as well as one fasted blood sample on the last morning. After a wash-out period of at least 1 week, participants will ingest a moderately high-oxalate (250-300 mg/day) fixed diet for 4 consecutive days and collect two 24-hr urines and a stool sample after 2 days of dietary equilibration, as well as one fasted blood sample on the last morning. Follow-up phase Participants will be followed up every 6 months to assess sustainability of colonization, provide a stool sample and answer a simple questionnaire. A 24-hr urine collection will be requested once a year after colonization, on the same moderately high oxalate diet diet after 2 days of dietary equilibration.
Interventions
DIETARY_SUPPLEMENTLow oxalate fixed diets pre-colonization
4 days of fixed eucaloric diet with low oxalate (\< 60 mg/day), normal calcium (600-1000 mg/day)
DIETARY_SUPPLEMENTModerately high oxalate fixed diets pre-colonization
4 days of fixed eucaloric diet with moderately high oxalate (250-300 mg/day), normal calcium (600-1000 mg/day)
DIETARY_SUPPLEMENTColonization with Oxalobacter formigenes
Ingestion of live Oxalobacter formigenes
DIETARY_SUPPLEMENTLow oxalate fixed diets post-colonization
4 days of fixed eucaloric diet with low oxalate (\< 60 mg/day), normal calcium (600-1000 mg/day)
DIETARY_SUPPLEMENTModerately high oxalate fixed diets post-colonization
4 days of fixed eucaloric diet with moderately high oxalate (250-300 mg/day), normal calcium (600-1000 mg/day)
Sponsors
University of Alabama at Birmingham
University of Texas Southwestern Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* age 19-70 yrs * Body Mass Index \> 18.5 kg/m2 * First time or recurrent Calcium Oxalate stone former. Composition of most recent stone ≥ 50% calcium oxalate if available * Not colonized with Oxalobacter formigenes * 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 fixed diet phases. * If on medications for stone prevention (e.g. thiazides, citrate, allopurinol), stable dose regimen for at least 2 weeks prior to and during study
Exclusion criteria
* Chronic Kidney Disease stage 4-5 * Primary hyperoxaluria * Liver, 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, Cystinuria, Uric acid stone former, Nephrotic syndrome, Sarcoidosis, Renal tubular acidosis, Primary hyperparathyroidism, Neurogenic bladder, Urinary diversion * 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 * Current Colonization with Oxalobacter formigenes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in urinary oxalate excretion following colonization with Oxalobacter formigenes | 2 months | Difference between urinary oxalate excretion on the moderately high oxalate diet pre-colonization and urinary oxalate excretion on the moderately high oxalate diet post-colonization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustainability of colonization with Oxalobacter formigenes | 4 years | duration of colonization after successful induction of colonization sith Oxalobacter formigenes |
Countries
United States
Contacts
CONTACTSonia Fargue, PhD
CONTACTDemond Wiley
PRINCIPAL_INVESTIGATORSonia Fargue, PhD
University of Alabama at Birmingham
Outcome results
None listed