Fecal Microbiota Transplantation in Kidney Stone Patients

Kidney Stones Clinical Trial

— FMT IND  

Official title:

Fecal Microbiota Transplantation (FMT CAPSULE DE, FMPCapDE, MTP-CP101) in Kidney Stone Patients (FMT IND STUDY)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05516472
• Other study ID #: 1051917
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 2024
• Est. completion date: March 2027

Study information

• Verified date: February 2024
• Source: Intermountain Health Care, Inc.
• Contact: Anika Isom
• Phone: 801-507-9292
• Email: anika.isom[@]imail.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

In this study, urinary stone disease patients will be recruited from the Park City Urology Clinic at Intermountain Healthcare. Subjects will undergo screening and baseline assessments, including a history and physical exam. A 24-hour urine sample will be collected. Urinary parameters include analysis for calcium, oxalate, uric acid, citrate, NH4, sulfate, pH, Cr, phosphate, sodium, potassium, magnesium, super saturation (SS) CaOx, SSUA, SSCaP, UUN. Microbial Transplant Therapy (MTT), the intervention, will be offered to individuals who produce greater than 60% calcium-oxalate stones. Pathology reports in the patient's medical record will be used to confirm the stone composition. The cohort of 36 total enrollees will be comprised of four separate study groups. The first group of 12 will include hyperoxaluric patients, the second group of 12 will include hypercalciuric patients, the third group will enroll six patients with hyperoxaluria as a control group, and the fourth group will enroll six patients with hypercalciuria as a control group. Grouping will be determined by 24-hour urine analysis which show measurements of urinary calcium >225mg/day (hypercalciuric group) and oxalate >40mg/day (hyperoxaluric group). Stool samples will be obtained for metagenomic analyses prior to the intervention. Subjects will be assigned to the hypercalciuric and hyperoxaluric arms based upon urine parameters or placed in the control arm by random assignment. Because antibiotic treatment is common during surgery for stones, participants will be treated with 3 days of vancomycin 500 mg orally twice a day and neomycin 1,000 mg orally twice a day. This treatment is for all subjects, rather than only for subjects with recent or planned urological intervention; in order for the MTT to take hold, all patients must be treated with antibiotics. Twenty-four hours later, participants will take either the control capsule or the microbial capsules, 2 capsules daily for 7 days.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: March 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

1. Women and men age >18 and <70

2. Recent medical history of USD with >60% calcium-oxalate stones. All patients will have urinary stone disease confirmed by stone analysis. The study will include patients with either stones extracted by urological intervention or spontaneously passed and collected stones. We will enroll recurrent urinary stone formers who have had a stone event in the preceding 24 months, but no sooner than within 4 weeks if they did not receive antibiotics and not after three months if they did receive antibiotics.

3. 24-hour urinary calcium concentration >225 mg/day or urinary oxalate >40 mg/day

4. Able to give informed consent.

5. Willing to undergo telephone follow-up to assess for safety and adverse events

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

7. Not actively participating in another interventional USD clinical trial

8. Estimated Glomerular Filtration Rate (eGFR) greater than or equal to 60.

Exclusion Criteria:

1. Presence of features of metabolic syndrome as defined by the NIH to have 3 or more of

the following conditions:

1. Large waist - A waistline that measures at least 35 inches (89 centimeters) for women and 40 inches (102 centimeters) for men

2. High triglyceride level - 150 milligrams per deciliter (mg/dL), or 1.7 millimoles per liter (mmol/L), or higher of this type of fat found in blood

3. Reduced "good" or HDL cholesterol - Less than 40 mg/dL (1.04 mmol/L) in men or less than 50 mg/dL (1.3 mmol/L) in women of high-density lipoprotein (HDL) cholesterol

4. Increased blood pressure - 130/85 millimeters of mercury (mm Hg) or higher

5. Elevated fasting blood sugar - 100 mg/dL (5.6 mmol/L) or higher

2. Presence of features of autoimmunity 3. Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy 4. Diagnosis of inflammatory bowel disease 5. Patient diagnosed with primary hyperparathyroidism. Any patient with a PTH outside the range of 11 - 51 pg/ml will be excluded.

6. Patient diagnosed secondary hyperparathyroidism. Any patient with a PTH outside the range of 11 - 51 pg/ml will be excluded.

7. All patients requiring pancreatic enzyme replacement will be excluded. 8. All patients diagnosed with colonic polyps on a diagnostic colonoscopy will be excluded.

9. Patient with ongoing dialysis treatment 10. Received chemotherapy treatment in the last 1 year 11. Treatment with antibiotics within 3 months of study entry 12. Patients taking potassium citrate, thiazides, or proton pump inhibitors in the last 6 months 13. Women who are pregnant or breast-feeding or planning to get pregnant during the time of the study.

14. Inability (e.g. dysphagia) to or unwilling to swallow capsules. Subjects with Grade greater than or equal to 2 dysphagia- as per Current Terminology for Common Adverse Events (CTCAE v 5.0) will be excluded.

15. Active gastrointestinal infection at time of enrollment 16. Requires continued antibiotic use or anticipates antibiotic use in the upcoming 4 weeks 17. Known or suspected toxic megacolon and/or known small bowel ileus 18. History of total colectomy or bariatric surgery 19. Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy 20. Expected life expectancy < 6 months 21. Previous FMT or microbiome-based products at any time excluding this study 22. Patients with a history of severe anaphylactic or anaphylactoid food allergy 23. Solid organ transplant recipients (all patients with a history of solid organ transplant will be excluded).

24. A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study.

25. Subjects will be excluded if they have chronic kidney disease defined as GFR (Glomerular Filtration Rate) less than 60.

26. Subjects with urinary oxalate greater than or equal to 80 mg/d will be excluded

Related Conditions & MeSH terms

• Kidney Calculi
• Kidney Stones
• Nephrolithiasis

Intervention

Drug:
• Microbial Transplant Therapy
Participants will take microbial capsules, 2 capsules daily for 7 days
• Placebo
Participants will take placebo capsules

Locations

Country	Name	City	State
United States	Park City Hospital	Park City	Utah

Sponsors (4)

Lead Sponsor	Collaborator
Joshua Stern	Albert Einstein College of Medicine, Litholink Corporation, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in 24 hour urinary oxalate concentration		Baseline to weeks 3, 4, and 5
Primary	Changes in 24 hour urinary calcium concentration		Baseline to week 3, 4, and 5
Primary	Proportion of participants with an adverse event		Baseline to day 30 (plus or minus 3 days) after fecal transplant
Secondary	Metagenomic changes to subject microbiota pre-MTT		Prior to fecal transplant (baseline)
Secondary	Metagenomic changes to subject microbiota post-MTT		weeks 4 and 5 after MTT