Clinical trial NCT06330246: O. Formigenes Colonization in Calcium Oxalate Kidney Stone Disease
Official title: Oxalobacter Formigenes Colonization in Calcium Oxalate Kidney Stone Formers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Stone
Kidney Calculi
Urolithiasis
Urolithiasis, Calcium Oxalate
Nephrolithiasis
Nephrolithiasis, Calcium Oxalate
Oxalate Urolithiasis
Oxaluria
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: University of Texas Southwestern Medical Center
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2024-03-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Change in urinary oxalate excretion following colonization with Oxalobacter formigenes
timeFrame: 2 months
Secondary outcomes:
measure: Sustainability of colonization with Oxalobacter formigenes
timeFrame: 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Dallas
country: United States
facility: UTSW
state: Texas
Study officials:
affiliation: University of Alabama at Birmingham
name: Sonia Fargue, PhD
role: PRINCIPAL_INVESTIGATOR
References: