Gut Bacteria for Kidney Stones

Recruiting at 1 trial location

Overseen By Demond Wiley

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must be taking: Thiazides, Citrate, Allopurinol

Must not be taking: Immunosuppressive medication

Disqualifiers: Chronic kidney disease, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether adding a specific gut bacteria, Oxalobacter formigenes, can reduce oxalate levels in urine, potentially preventing painful kidney stones. Participants will use this live bacteria preparation to see if it helps prevent calcium oxalate kidney stones. The study seeks adults who have had calcium oxalate kidney stones and do not already carry this bacteria. Participants should be comfortable with dietary changes and must avoid certain supplements during the trial period. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new prevention strategies for kidney stones.

Will I have to stop taking my current medications?

The trial requires participants to stop taking supplements like vitamins, calcium, and probiotics for 2 weeks before and during the diet phases. If you are on medications for kidney stone prevention, you must be on a stable dose for at least 2 weeks before and during the study.

What prior data suggests that colonization with Oxalobacter formigenes is safe for humans?

Research has shown that using Oxalobacter formigenes is generally safe for people. One study found that taking this bacteria is safe and helps it settle in the gut, allowing it to live in the digestive system without causing harm. Another study demonstrated that oral intake of Oxalobacter formigenes significantly reduced oxalate levels (a chemical that can form kidney stones) in urine and blood.

These findings suggest that Oxalobacter formigenes is well-tolerated and does not cause serious side effects. While research supports its safety, discussing any concerns with a healthcare professional before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for kidney stones, which often involve pain management, dietary changes, or surgical procedures, Oxalobacter formigenes acts on the problem at its root by using a live bacterial strain to naturally break down oxalate in the gut. This approach is unique because it targets the cause of kidney stone formation rather than just managing the symptoms or removing the stones. Researchers are excited about this treatment because it potentially offers a preventive solution, reducing the risk of stone formation by altering the gut microbiome.

What evidence suggests that colonization with Oxalobacter formigenes is effective for reducing urinary oxalate excretion in calcium oxalate kidney stone disease?

In this trial, participants will receive Oxalobacter formigenes, a gut bacteria linked in previous studies to a 70% reduction in the risk of forming calcium oxalate kidney stones. This bacteria helps break down oxalate, a substance in some foods that can cause kidney stones when it accumulates in the body. Research has shown that people with Oxalobacter formigenes in their gut tend to experience fewer recurring stones. Some studies suggest that adding this bacteria can lower the chance of developing new stones. Overall, Oxalobacter formigenes appears to protect against kidney stones. ^{1 2 6 7 8}

Who Is on the Research Team?

Sonia Fargue, M.D., Ph.D.

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Adults with a history of calcium oxalate kidney stones who currently do not have the gut bacteria Oxalobacter formigenes. Participants will need to follow strict diets and provide urine, blood, and stool samples.

Inclusion Criteria

I am willing to stop taking vitamins, minerals, and supplements for 2 weeks before and during the diet phases.

Body Mass Index > 18.5 kg/m2

Willing to ingest fixed diets

Exclusion Criteria

I have been diagnosed with primary hyperoxaluria.

Pregnancy or breast-feeding

My kidney function is severely reduced.

Timeline for a Trial Participant

Screening and Pre-colonization

Participants are screened for eligibility to participate in the trial, including stool colonization testing, blood complete metabolic profile, 24-hr urine specimens collected at home on self-selected diets and anthropometric measurements.

2-4 weeks

1 visit (in-person) for screening, home collections

Colonization and Post-colonization

Participants are colonized with Oxalobacter formigenes and follow a fixed diet to measure urinary oxalate excretion before and after colonization.

2 months

Multiple visits for sample collection and diet adherence

Follow-up

Participants are monitored every 6 months to assess sustainability of colonization, provide a stool sample, and answer a questionnaire. A 24-hr urine collection is requested once a year.

4 years

Biannual visits (in-person or virtual), annual urine collection

What Are the Treatments Tested in This Trial?

Interventions

• Oxalobacter formigenes

Trial Overview The trial is testing whether introducing Oxalobacter formigenes into patients can lower urinary oxalate levels. It involves fixed diets with varying oxalate levels before and after colonization with the bacteria.

How Is the Trial Designed?

Group I: colonization with Oxalobacter formigenes Experimental Treatment 5 Interventions

Colonization with a live preparation of Oxalobacter formigenes, strain OxCC13.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 76 children and adolescents with calcium oxalate urolithiasis, only 27.6% were colonized with the bacterium Oxalobacter formigenes, similar to the 26% colonization rate in healthy controls.

Children with calcium urolithiasis who were colonized with O. formigenes had significantly lower urinary oxalate excretion compared to those who were not colonized, suggesting that the absence of this bacterium may contribute to higher oxalate levels and increased risk of kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal colonization with Oxalobacter formigenes and its relation to urinary oxalate excretion in pediatric patients with idiopathic calcium urolithiasis. Sikora, P., Niedźwiadek, J., Mazur, E., et al.[2018]

Transplanting human feces along with the O. formigenes strain into mice successfully established stable colonization of these bacteria for at least 8 weeks, indicating a potential model for studying their effects on kidney stone risk.

The humanization process significantly altered the gut microbiome of the mice, suggesting that O. formigenes can integrate into and modify the intestinal microbial community, which may help in identifying effective strains for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization. Pebenito, AM., Liu, M., Nazzal, L., et al.[2020]

This study found no causal link between the gut bacterium Oxalobacter formigenes and the formation of kidney stones, suggesting that its presence does not significantly influence kidney stone development.

However, other gut microbiota, such as certain genera and families, were identified as either protective or risk factors for kidney stones, indicating a more complex relationship that warrants further investigation using advanced research methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Causal relationship between kidney stones and gut microbiota contributes to the gut-kidney axis: a two-sample Mendelian randomization study. Liu, M., Zhang, Y., Wu, J., et al.[2023]

In a study using male Sprague-Dawley rats with induced hyperoxaluria, treatment with the bacterium Oxalobacter formigenes significantly reduced urinary oxalate levels within just 2 days, with greater reductions observed at higher doses.

The probiotic treatment was found to be safe, as the rats showed no signs of toxicity or health issues, suggesting that O. formigenes could be a promising option for managing calcium oxalate kidney stone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. Sidhu, H., Allison, MJ., Chow, JM., et al.[2017]

Oxalobacter formigenes, a gut bacterium, helps break down oxalate, which can lower urinary oxalate levels and potentially reduce the risk of kidney stones, particularly those made of calcium oxalate.

The review highlights the impact of antibiotics on the colonization of Oxalobacter formigenes and suggests that probiotics and whole microbial communities could be explored as possible treatments for kidney stone disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the microbiome in kidney stone formation. Mehta, M., Goldfarb, DS., Nazzal, L.[2018]

In a study of 103 patients with calcium oxalate stone disease, 45.6% were found to have intestinal colonization of Oxalobacter formigenes, which is associated with lower urinary oxalate levels.

The presence of O. formigenes in the gut was linked to a significant decrease in urinary oxalate excretion, suggesting that this bacterium plays a crucial role in maintaining oxalate balance and may help reduce the risk of kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary oxalate levels and the enteric bacterium Oxalobacter formigenes in patients with calcium oxalate urolithiasis. Kwak, C., Kim, HK., Kim, EC., et al.[2022]

The presence of the bacterium Oxalobacter formigenes in the intestine can help reduce urinary oxalate levels, which lowers the risk of developing calcium oxalate kidney stones.

The genome sequence of a specific strain, Oxalobacter formigenes SSYG-15, was obtained from a healthy individual, providing valuable genetic information that could enhance our understanding of its beneficial effects on kidney stone prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome Sequence of Oxalobacter formigenes Strain SSYG-15. Sun, NY., Gao, Y., Yu, HJ.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2396938/

Oxalobacter formigenes May Reduce the Risk of Calcium ... formigenes is associated with a 70% reduction in the risk for being a recurrent calcium oxalate stone former. Kidney stones represent an important health ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925000932

Inducing Oxalobacter formigenes Colonization Reduces ... Kaufman and colleagues also demonstrated that colonization was associated with a reduced risk of developing recurrent calcium oxalate kidney stones. Rodent ...

3. brieflands.com brieflands.com/journals/num/articles/115769

The Effect of Oxalobacter formigenes Colonization in ... Results: We found that the presence of O. formigenes could reduce the risk of kidney stones and calcium oxalate stones. In fact, both FRC and OXC ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5764756/

The role of the microbiome in kidney stone formation - PMC In this review, we examine the data studying the role of Oxalobacter formigenes in kidney stone disease in humans and animals, the effect of antibiotics on ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06330246?cond=oxaluria%20OR%20%22sialuria,%20French%20type%22&aggFilters=status:not%20rec&viewType=Table&rank=1&checkSpell=

O. Formigenes Colonization in Calcium Oxalate Kidney ... 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 ...

6. nature.com nature.com/articles/ncpneph0812-nrurol

Absence of Oxalobacter formigenes is associated with ... O. formigenes colonization was less prevalent among patients with kidney stones than among controls (17% vs 38%, multivariate odds ratio 0.3, 95% CI 0.2– ...

7. academic.oup.com academic.oup.com/ndt/article-abstract/26/11/3609/1829943

Efficacy and safety of Oxalobacter formigenes to reduce ... Orally administered O. formigenes (Oxabact) was found to significantly reduce urine and plasma oxalate. We aimed to evaluate its effect and safety in a ...

8. kidney-international.org kidney-international.org/article/S0085-2538%2815%2955877-8/fulltext

A new era in the treatment of calcium oxalate stones? Excessive urinary concentrations of oxalate and calcium lead to development of calcium oxalate kidney stones. Oxalobacter formigenes is destroying oxalic acid ...