Fecal Microbiota Transplantation for Kidney Stones

(FMT IND Trial)

Overseen By Joshua Stern, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Joshua Stern

Must not be taking: Potassium citrate, Thiazides, PPIs

Disqualifiers: Metabolic syndrome, Autoimmunity, IBD, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

36 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure the impact of Microbial Transplant Therapy (MTT) on 24-hour urine parameters in recurrent hypercalciuric and hyperoxaluric kidney stone formers.

Will I have to stop taking my current medications?

The trial requires that participants have not taken potassium citrate, thiazides, or proton pump inhibitors in the last 6 months. Additionally, you cannot have taken antibiotics within 3 months before the study or require continued antibiotic use during the study.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation for Kidney Stones?

Fecal Microbiota Transplantation (FMT) has shown effectiveness in treating recurrent Clostridium difficile infections and ulcerative colitis by introducing healthy bacteria into the gut, which suggests it might help with other conditions by improving gut health and immune function. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe for treating recurrent Clostridium difficile infections, but there are still challenges with adverse events (unwanted side effects) and donor screening. More research is needed to confirm its safety for other conditions. ^{6 7 8 9 10}

How is fecal microbiota transplantation different from other treatments for kidney stones?

Fecal microbiota transplantation (FMT) is unique because it involves transferring a whole community of gut bacteria, which can degrade oxalate, a major component of most kidney stones. This approach targets the gut microbiome to reduce stone formation, unlike traditional treatments that focus on managing symptoms or removing stones. ^{11 12 13 14 15}

Research Team

Joshua Stern, MD

Principal Investigator

Intermountain Health Care, Inc.

Eligibility Criteria

This trial is for adults aged 18-70 with a history of kidney stones, specifically those with high levels of calcium or oxalate in their urine. Participants must have had a stone event within the last two years and be able to perform study tasks like urine collection. Exclusions include individuals on dialysis, recent chemotherapy patients, those who've had certain surgeries or gastrointestinal conditions, pregnant women, and others with specific health issues.

Inclusion Criteria

Not actively participating in another interventional USD clinical trial

Willing and able to participate in the study requirements, including study visits, 24-hour urine collection and serial stool collection

I agree to phone calls to check on my health and side effects.

Exclusion Criteria

I have been diagnosed with metabolic syndrome.

I have had chemotherapy in the past year.

I have not taken antibiotics in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline assessments including history, physical exam, and 24-hour urine sample collection

1 week

1 visit (in-person)

Run-in Period

Initial treatment of 7-10 patients to begin the study

1-2 weeks

Randomization and Treatment

Participants are randomized into treatment or control groups and receive antibiotics followed by capsules

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Microbial Transplant Therapy
• Placebo

Trial Overview The trial is testing Microbial Transplant Therapy (MTT) against a placebo to see its effects on urinary factors related to kidney stone formation. Participants will either receive MTT or an inactive substance without knowing which one they're getting.

Participant Groups

Group I: Hyperoxaluric group Experimental Treatment 1 Intervention

Treatment group based on 24 hour urine analysis showing oxalate \>40 mg/day.

Group II: Hypercalciuric Group Experimental Treatment 1 Intervention

Treatment group based on 24 hour urine analysis showing urinary calcium \>225 mg/day.

Group III: Control group Hyperoxaluria Placebo Group 1 Intervention

Control group enrolling patients with hyperoxaluria

Group IV: Control group Hypercalciuria Placebo Group 1 Intervention

Control group enrolling patients with hypercalciuria

Microbial Transplant Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection

Approved in Canada as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection

Who Is Running the Clinical Trial?

Joshua Stern

Lead Sponsor

Trials

1

Recruited

40+

Litholink Corporation

Collaborator

Trials

1

Recruited

40+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

Albert Einstein College of Medicine

Collaborator

Trials

302

Recruited

11,690,000+

Litholink Corp

Collaborator

Trials

1

Recruited

40+

Findings from Research

Fecal microbial transplantation (FMT) is an effective treatment for recurrent Clostridium difficile colitis, with various delivery methods such as oral ingestion, colonoscopy, and enemas tailored to patient needs.

Careful selection of donors and patients is essential to ensure safety and efficacy, as FMT is being explored for potential treatment of other conditions beyond just C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Aspects of Fecal Microbial Transplantation (FMT). Bhutiani, N., Schucht, JE., Miller, KR., et al.[2018]

A kidney transplant recipient successfully treated recurrent urinary tract infections with fecal microbiota transplantation (FMT), remaining symptom-free after the procedure.

The study highlights the need for further research to understand the underlying mechanisms of how FMT works in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. Biehl, LM., Cruz Aguilar, R., Farowski, F., et al.[2019]

Fecal microbial transplantation (FMT) can lead to complex changes in the gut microbial community, with patterns of dominance shifting between donor and recipient strains over time, as observed in a study analyzing samples from 5 FMTs over up to 535 days.

The study identified potential recombination events between donor and recipient strains, particularly in Bacteroides vulgatus, suggesting that FMT not only introduces new microbes but can also lead to interactions that may affect gut metabolism and immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains. Koo, H., Morrow, CD.[2022]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

In a study of 30 patients with ulcerative colitis who did not respond to standard treatments, 70% showed a clinical response to fecal microbial transplantation (FMT) after 12 weeks, with 43.3% achieving both clinical and endoscopic remission.

FMT was found to be a safe alternative to immunosuppressive therapies, with only mild adverse events reported in 23.3% of patients, suggesting it could be a promising option for those with refractory ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. Uygun, A., Ozturk, K., Demirci, H., et al.[2018]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

Fecal microbiota transplantation (FMT) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infections, and research is expanding to explore its potential for treating other conditions related to chronic inflammation and autoimmunity.

Current studies on FMT for conditions like ulcerative colitis and metabolic syndrome show promise, but many lack rigorous methodology, highlighting the need for more standardized and well-designed trials to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. Gilbert, B., Schrenzel, J.[2019]

Fecal microbiota transplantation (FMT) successfully induced and maintained clinical remission in a patient with ulcerative colitis (UC) who was allergic to 5-aminosalicylic acid (5-ASA), demonstrating its potential as an alternative treatment.

This case highlights the efficacy of FMT in reconstructing intestinal microbiota for patients with refractory UC, especially when conventional treatments like steroid therapy fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report. Wang, HG., Liu, SP., Ma, TH., et al.[2021]

A study screened 2071 potential stool donors for fecal microbiota transplantation (FMT) in China, resulting in a low selection rate of 3.19%, highlighting the challenges in finding suitable donors.

The research established a donor microbial evaluation index (DoMEI) to improve the screening process, ensuring safety and stability of gut microbiota, which is crucial for the effectiveness of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive approach to stool donor screening for faecal microbiota transplantation in China. He, J., He, X., Ma, Y., et al.[2022]

Fecal microbiome transplantation (FMT) in male guinea pigs and Sprague-Dawley rats significantly reduced urinary oxalate levels and calcium oxalate crystal deposition in the kidneys, suggesting a potential therapeutic role for FMT in preventing kidney stones.

The study identified a beneficial microbial network activated by FMT, including bacteria like Muribaculaceae and Lactobacillus, which enhanced intestinal oxalate degradation and may provide a protective effect against oxalate-related kidney damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats. Wang, Y., Sun, J., Xie, S., et al.[2023]

Fecal transplants from Zucker lean rats to germ-free mice significantly reduced urinary calcium by 55% and urinary oxalate levels by 24%, suggesting that gut microbiome composition can influence urinary stone disease risk factors.

The study found a 90% increase in the expression of the Slc26a6 transporter, which is involved in oxalate balance, indicating that the gut microbiome may play a crucial role in metabolic processes that affect urinary chemistry and stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal transplant modifies urine chemistry risk factors for urinary stone disease. Stern, JM., Urban-Maldonado, M., Usyk, M., et al.[2023]

About 80% of kidney stones are made of calcium oxalate, and the gut microbiome may influence their formation and prevention.

Specific gut bacteria, such as Oxalobacter formigenes, Bifidobacterium, and Lactobacillus, are linked to calcium oxalate stones, suggesting that modifying gut flora could be a new approach to prevent kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of intestinal flora on calcium oxalate stones. Wang, C., Dong, X., Yin, X., et al.[2021]

Oxalobacter formigenes, a known oxalate-degrading bacterium, does not effectively predict the risk of urinary stone disease (USD) or urinary oxalate levels, suggesting limitations in current probiotic approaches.

A meta-analysis revealed that shifts in the overall gut microbiota are significantly associated with USD, indicating that effective bacteriotherapy should target a diverse range of gut bacteria rather than just a few specific species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium Oxalate Urolithiasis: A Case of Missing Microbes? Batagello, CA., Monga, M., Miller, AW.[2019]

Oxalobacter formigenes, a beneficial bacterium that helps prevent calcium oxalate kidney stones, was found in only 31% of healthy young adults in the U.S., indicating that it is not present in the majority of this population.

When O. formigenes was detected, it showed a high stability of colonization, with 93% of individuals remaining positive for the bacterium at follow-up visits, suggesting its potential role in long-term kidney stone prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Presence of Oxalobacter formigenes in the Microbiome of Healthy Young Adults. Barnett, C., Nazzal, L., Goldfarb, DS., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Technical Aspects of Fecal Microbial Transplantation (FMT). [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report. [2021]

10. England pubmed.ncbi.nlm.nih.gov

A comprehensive approach to stool donor screening for faecal microbiota transplantation in China. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Fecal transplant modifies urine chemistry risk factors for urinary stone disease. [2023]

13. China pubmed.ncbi.nlm.nih.gov

Impact of intestinal flora on calcium oxalate stones. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Calcium Oxalate Urolithiasis: A Case of Missing Microbes? [2019]

15. United States pubmed.ncbi.nlm.nih.gov

The Presence of Oxalobacter formigenes in the Microbiome of Healthy Young Adults. [2018]