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

Oxalobacter Formigenes Colonization and Urinary Oxalate Excretion

Sponsors

Lead sponsor: University of Alabama at Birmingham

Source University of Alabama at Birmingham
Brief Summary

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

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). Each subject will perform a sodium 13C2-oxalate oral load once at the end of each of the two dietary phases to assess dietary oxalate absorption. 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.

Overall Status Recruiting
Start Date April 2, 2018
Completion Date January 31, 2022
Primary Completion Date January 31, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Measurement of urinary oxalate by ion chromatography mass spectrometry 1st 24 hour collection
Measurement of urinary oxalate by ion chromatography mass spectrometry 2nd 24 hour collection
Measurement of urinary oxalate by ion chromatography mass spectrometry 3rd 24 hour collection
Measurement of urinary oxalate by ion chromatography mass spectrometry 4th 24 hour urine collection
Secondary Outcome
Measure Time Frame
Measurement of stool oxalate by ion chromatography mass spectrometry Stool collected 48-96 hours post diet
Measurement of stool oxalate by ion chromatography mass spectrometry Stool collected 48-96 hours post diet
Measurement of stool oxalate by ion chromatography mass spectrometry Stool collected 48-96 hours post diet
Measurement of plasma oxalate by ion chromatography coupled with mass spectrometry Fasted plasma 4 days post diet
Enrollment 20
Condition
Intervention

Intervention type: Other

Intervention name: Low Oxalate Diet

Description: Subjects will be instructed to ingest a controlled diet low in oxalate

Arm group label: Low Oxalate Diet

Intervention type: Other

Intervention name: Moderately high oxalate/low calcium diet

Description: Subjects will be instructed to ingest a controlled diet moderately high in oxalate

Arm group label: Moderately high oxalate/low calcium diet

Intervention type: Other

Intervention name: Oxalobacter formigenes

Description: Subjects will ingest liver preparation of O. formigenes

Arm group label: Oxalobacter formigenes

Eligibility

Criteria:

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

Gender: All

Minimum age: 19 Years

Maximum age: 65 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
John Knight, PhD Principal Investigator University of Alabama at Birmingham
Overall Contact

Last name: John Knight, PhD

Phone: 205-996-2295

Email: [email protected]

Location
facility status contact investigator University of Alabama at Birmingham Demond Wiley [email protected] John Knight, PhD Principal Investigator Ross P Holmes, PhD Sub-Investigator Dean G Assimos, MD Sub-Investigator Robert A Oster, PhD Sub-Investigator
Location Countries

United States

Verification Date

February 2020

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: University of Alabama at Birmingham

Investigator full name: John Knight

Investigator title: Associate Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Low Oxalate Diet

Arm group type: Experimental

Description: Subjects not colonized with Oxalobacter formigenes will be equilibrated to a low oxalate diet to determine baseline oxalate values in urine and plasma. Subjects will be colonized with Oxalobacter formigenes (Intervention). Following colonization with Oxalobacter formigenes, urinary and plasma oxalate will be measured to determine the impact of colonization.

Arm group label: Moderately high oxalate/low calcium diet

Arm group type: Experimental

Description: 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 and plasma oxalate will be measured to determine the impact of colonization.

Arm group label: Oxalobacter formigenes

Arm group type: Experimental

Description: Subjects will ingest a liver preparation of O.formigenes

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Crossover Assignment

Intervention model description: Evaluate urinary oxalate excretion before and after colonization with the oxalate degrading bacterium Oxalobacter formigenes

Primary purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov