O. Formigenes Colonization in Calcium Oxalate Kidney Stone Disease

The University of Alabama at Birmingham

Status

Enrolling

Conditions

Oxaluria

Urolithiasis

Kidney Stone

Oxalate Urolithiasis

Nephrolithiasis, Calcium Oxalate

Nephrolithiasis

Urolithiasis, Calcium Oxalate

Kidney Calculi

Treatments

Dietary Supplement: Low oxalate fixed diets pre-colonization

Dietary Supplement: Moderately high oxalate fixed diets post-colonization

Dietary Supplement: Low oxalate fixed diets post-colonization

Dietary Supplement: Moderately high oxalate fixed diets pre-colonization

Dietary Supplement: Colonization with Oxalobacter formigenes

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06330246

R01DK137784 (U.S. NIH Grant/Contract)

IRB300005280

Details and patient eligibility

About

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

Full 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.

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.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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