Oxalobacter Formigenes Colonization and Urinary Oxalate Excretion

Study Overview
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Brief Summary
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The purpose of this research study is to assess the efficacy of ingesting a small amount of the harmless bacterium Oxalobacter formigenes in establishing residence in the guts of human subjects and to determine whether this influences the oxalate passed in urine of healthy volunteers.

Detailed Description
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Adults that are not colonized with O. formigenes, have no history of stone disease and are in good health as judged by their medical history, a complete metabolic profile of their serum, and ranges of ions that influence stone formation in two 24-hour urine collections, will be recruited from within the greater Birmingham area. Recruited subjects will be between the ages of 18 to 65 years and with a BMI >19 and <32. Subjects not colonized with O. formigenes will consume, firstly, a controlled diet containing 50 mg oxalate and 1000mg calcium (low oxalate/normal calcium diet), followed by a 250 mg oxalate/400mg calcium controlled diet (moderately high oxalate/low calcium diet), with at least a one week washout between each diet, and then repeat the same sequence of diets after colonization with O.formigenes Group 1 strain OxCC13. Controlled diets will be prepared in the Metabolic Kitchen of the UAB Clinical Research Unit (CRU). Sustainability of colonization will be determined over time. Loss of colonization will be confirmed by having the subject consume an oxalate-rich meal with subsequent testing for O. formigenes.

Official Title
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Oxalobacter Formigenes Colonization and Oxalate Excretion in Calcium Oxalate Kidney Stone Disease

Conditions
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Calcium Oxalate Urolithiasis

Intervention / Treatment
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* Other: Low Oxalate Diet
* Other: Moderately high oxalate/low calcium diet
* Other: Oxalobacter formigenes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good health as judged from a medical history and reported medications Not colonized with O. formigenes Exclusion Criteria: History of any hepatic, renal, bowel or endocrine disease or any other condition that may influence the absorption, transport or urinary excretion of ions, which will compromise the interpretation of results colonized with O. formigenes abnormal urine chemistries or blood metabolic profiles

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Evaluate urinary oxalate excretion before and after colonization with the oxalate degrading bacterium Oxalobacter formigenes
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Oxalate Diet<br>Subjects not colonized with Oxalobacter formigenes will be equilibrated to a low oxalate diet to determine baseline oxalate values in urine . Subjects will be colonized with Oxalobacter formigenes (Intervention). Following colonization with Oxalobacter formigenes, urinary oxalate will be measured to determine the impact of colonization. | Other: Low Oxalate Diet<br>* Subjects will be instructed to ingest a controlled diet low in oxalate<br>|
| Experimental: Moderately high oxalate/low calcium diet<br>Subjects not colonized with Oxalobacter formigenes will be equilibrated to a moderately high oxalate/ low calcium oxalate diet to enhance dietary oxalate absorption. Subjects will be colonized with Oxalobacter formigenes(Intervention). Following colonization with Oxalobacter formigenes, urinary oxalate will be measured to determine the impact of colonization. | Other: Moderately high oxalate/low calcium diet<br>* Subjects will be instructed to ingest a controlled diet moderately high in oxalate<br>|
| Experimental: Oxalobacter formigenes<br>Subjects will ingest a live preparation of O.formigenes | Other: Oxalobacter formigenes<br>* Subjects will ingest live preparation of O. formigenes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of urinary oxalate by ion chromatography mass spectrometry | 1st 24 hour urine collection, started 24 hours after initiation of controlled diet | 1st 24 hour collection | 
| Measurement of urinary oxalate by ion chromatography mass spectrometry | 48 hours post diet | 2nd 24 hour collection | 
| Measurement of urinary oxalate by ion chromatography mass spectrometry | 72 hours post diet | 3rd 24 hour collection | 
| Measurement of urinary oxalate by ion chromatography mass spectrometry | 96 hours post diet | 4th 24 hour urine collection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of stool oxalate by ion chromatography mass spectrometry | First bowel movement collected during days 2 through 4 of dietary control | Stool collected 48-96 hours post diet | 
| Measurement of stool oxalate by ion chromatography mass spectrometry | Second bowel movement collected during days 2 through 4 of dietary control | Stool collected 48-96 hours post diet | 
| Measurement of stool oxalate by ion chromatography mass spectrometry | Third bowel movement collected during days 2 through 4 of dietary control | Stool collected 48-96 hours post diet | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxalobacter formigenes, oxalate, kidney stones