O. Formigenes Colonization in Calcium Oxalate Kidney Stone Disease

Oxalobacter Formigenes Colonization in Calcium Oxalate Kidney Stone Formers

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

Study Overview

• Status: Recruiting
• Conditions: Kidney Calculi; Nephrolithiasis; Urolithiasis; Kidney Stone; Nephrolithiasis, Calcium Oxalate; Oxaluria; Urolithiasis, Calcium Oxalate; Oxalate Urolithiasis
• Intervention / Treatment: Dietary supplement: Low oxalate fixed diets pre-colonization; Dietary supplement: Moderately high oxalate fixed diets pre-colonization; Dietary supplement: Colonization with Oxalobacter formigenes; Dietary supplement: Low oxalate fixed diets post-colonization; Dietary supplement: Moderately high oxalate fixed diets post-colonization

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sonia Fargue, PhD; Phone Number: 2059756932; Email: sfargue@uab.edu
• Study Contact Backup: Name: Demond Wiley; Phone Number: 2059345712; Email: kidneystone@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Principal Investigator: Sonia Fargue, PhD
      • Contact: Sonia Fargue, PhD; Phone Number: 205-975-6932; Email: sfargue@uab.edu
      • Contact: Research Coordinator; Phone Number: 2059345712; Email: kidneystone@uabmc.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UTSW
      • Principal Investigator: Naim Maalouf, MD
      • Contact: Naim Maalouf, MD; Email: Naim.Maalouf@UTSouthwestern.edu
      • Contact: Esperanza Jackson; Email: Esperanza.Jackson@UTSouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: colonization with Oxalobacter formigenes; Colonization with a live preparation of Oxalobacter formigenes, strain OxCC13.

Dietary supplement: Low oxalate fixed diets pre-colonization; 4 days of fixed eucaloric diet with low oxalate (< 60 mg/day), normal calcium (600-1000 mg/day); Dietary supplement: Moderately 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 supplement: Colonization with Oxalobacter formigenes; Ingestion of live Oxalobacter formigenes; Dietary supplement: Low oxalate fixed diets post-colonization; 4 days of fixed eucaloric diet with low oxalate (< 60 mg/day), normal calcium (600-1000 mg/day); Dietary supplement: Moderately 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urinary oxalate excretion following colonization with Oxalobacter formigenes	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	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustainability of colonization with Oxalobacter formigenes	duration of colonization after successful induction of colonization sith Oxalobacter formigenes	4 years

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Sonia Fargue, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Calculi; Urolithiasis; Calculi; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: IRB300005280; R01DK137784 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No