Fecal Microbiota Transplantation as a Therapeutic Strategy in the Progression of Chronic Kidney Disease

Chronic Kidney Disease Due to Type 2 Diabetes Mellitus Clinical Trial

Official title:

Fecal Microbiota Transplantation as a Therapeutic Strategy in the Progression of Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04361097
• Other study ID #: IF18-00003
• Status: Completed
• Phase: N/A
• Start date: August 7, 2018
• Est. completion date: April 21, 2020

Study information

• Verified date: April 2020
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

What the investigators want to achieve with the protocol is to identify the impact of intestinal microbiota transplantation on the progression of chronic kidney disease.

Hypothesis: Modification of intestinal microbioma of CKD patients by TMF decrease the progression of CKD Methodological design: Experimental, prospective, double-blind. Inclusion criteria: Being diagnosed with CKD and creatinine clearance less than 60 mL/minute secondary hypertension and/or diabetes and older than 18 years

Description:

What the investigators want to achieve with the protocol is to identify that impact has transplantation intestinal microbiota on the progression of chronic kidney disease

A.-Hypothesis: Modification of intestinal microbioma of CKD patients by TMF decrease the progression of CKD.

B.-Specific objectives: Evaluate whether decreases TMF markers of inflammation in patients with CKD after being treated with TMF, evaluate the behavior in CKD progression markers in patients undergoing TMF, evaluate the change in bowel microbioma CKD patients before and after undergoing TMF.

C.-Methodological design: Experimental, prospective, double-blind.

D.-Type of study: Controlled clinical trial

E.- Population in study:

1. -Inclusion criteria: Being diagnosed with CKD and creatinine clearance less than 60 mL/minute secondary hypertension and/or diabetes, older than 18 years.

2. - Exclusion Criteria: Malignancies whose last treatment has been less than 5 years, he is receiving antibiotics for any reason during the month prior to enrollment, having received probiotics in the last 3 months, it has been diagnosed with Clostridium difficile infection in the last year, it has been previously subjected to TMF , exacerbations of submitting ERC during the 3 months prior or present at the time of enrollment.

3. -Criteria for elimination: Failure to comply in the structured patient monitoring, nondelivery of stool samples at set times, the patient decides to no longer participate in the study.

F.- Desing Description: After being selected and randomized patients who meet the criteria for inclusion and exclusion, they are assigned to a group to start treatment TMF (capsules intestinal microbiota frozen) or a group receive placebo capsules which shall consist of an excipient harmless to the body (capsules frozen saline), both will be developed in the service Infectología.

Both groups receive frozen for ingestion orally capsules (comprised of TMF or placebo according to the randomization) with a frequency of 15 capsules each 12hrs for 4 doses on days 1, 10 and 30 of the study. Each capsule must be ingested over a period no longer than 1 hour.

measurements characteristic factors of the progression of kidney disease day 0,10, 30, 60, 90, 120 and 180 be made consisting of:

• Proteins in urine 24 hours

• Creatinine clearance 24 hours

• CBC

• serum creatinine

• Urea Nitrogen

• Urea

• Glucose

• Uric acid

• IS

• venous gases

Blood samples were taken by puncture of peripheral vein by laboratory personnel to assess renal function, urine samples will be collected by the patient at home and transported to the laboratory, none of these samples will be used for genetic analysis , only samples of faeces they underwent genomic analysis, collection of stool samples will days 0, 5, 10 30, 90 and 180 (on 10, 30, 90 and 180 with a range of +/- 2 days).

adverse effects questionnaires on days 1, 5, 30 and 60 is performed and quality of life assessment on days 0, 10, 30, 90 and 180.

Monitoring will face on a weekly basis to register if they have submitted infections, adverse effects and whether changes have received treatment. Visits will be made in the epidemiology and the Regional Center for Kidney Diseases University Hospital

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 21, 2020
• Est. primary completion date: November 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Be diagnosed with CKD and creatinine clearance less than 60 ml / minute secondary to hypertension and / or diabetes.

• Age over 18 years

Exclusion Criteria:

• Malignant neoplasms whose last treatment was less than 5 years

• Having received antibiotics for any reason during the month prior to enrollment

• Have received probiotics in the last 3 months

• Have been diagnosed with Clostridium difficile infection in the last year

• Have been previously submitted to TMF

• Having presented ERC exacerbations during the 3 months prior or present at the time of enrollment

Related Conditions & MeSH terms

• Chronic Kidney Disease Due to Hypertension
• Chronic Kidney Disease Due to Type 2 Diabetes Mellitus
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Biological:
• Faecal microbiota transplant
Both groups will receive frozen capsules to be ingested orally (constituted of TMF or placebo according to the randomization) with a frequency of 15 capsules every 12hrs for 4 doses on days 1, 10 and 30 of the study. Each capsule should be ingested in a period no longer than 1 hour.
• Placebo
Both groups will receive frozen capsules to be ingested orally (constituted of TMF or placebo according to the randomization) with a frequency of 15 capsules every 12hrs for 4 doses on days 1, 10 and 30 of the study. Each capsule should be ingested in a period no longer than 1 hour.

Locations

Country	Name	City	State
Mexico	Hospital Universitario José E. Gonzalez	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (15)

Choi HH, Cho YS. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clin Endosc. 2016 May;49(3):257-65. doi: 10.5946/ce.2015.117. Epub 2016 Mar 9. Review. — View Citation

Cruz-Mora J, Martínez-Hernández NE, Martín del Campo-López F, Viramontes-Hörner D, Vizmanos-Lamotte B, Muñoz-Valle JF, García-García G, Parra-Rojas I, Castro-Alarcón N. Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease. J Ren Nutr. 2014 Sep;24(5):330-5. doi: 10.1053/j.jrn.2014.05.006. Epub 2014 Jul 22. — View Citation

Felizardo RJ, Castoldi A, Andrade-Oliveira V, Câmara NO. The microbiota and chronic kidney diseases: a double-edged sword. Clin Transl Immunology. 2016 Jun 10;5(6):e86. eCollection 2016 Jun. Review. — View Citation

Guida B, Germanò R, Trio R, Russo D, Memoli B, Grumetto L, Barbato F, Cataldi M. Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):1043-9. doi: 10.1016/j.numecd.2014.04.007. Epub 2014 May 2. — View Citation

Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature. 2016 Jul 7;535(7610):75-84. doi: 10.1038/nature18848. Review. — View Citation

Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW. Chronic kidney disease: global dimension and perspectives. Lancet. 2013 Jul 20;382(9888):260-72. doi: 10.1016/S0140-6736(13)60687-X. Epub 2013 May 31. Review. Erratum in: Lancet. 2013 Jul 20;382(9888):208. — View Citation

Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, Afzali A, Aroniadis O, Barto A, Borody T, Giovanelli A, Gordon S, Gluck M, Hohmann EL, Kao D, Kao JY, McQuillen DP, Mellow M, Rank KM, Rao K, Ray A, Schwartz MA, Singh N, Stollman N, Suskind DL, Vindigni SM, Youngster I, Brandt L. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014 Jul;109(7):1065-71. doi: 10.1038/ajg.2014.133. Epub 2014 Jun 3. — View Citation

Lin CJ, Wu V, Wu PC, Wu CJ. Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure. PLoS One. 2015 Jul 14;10(7):e0132589. doi: 10.1371/journal.pone.0132589. eCollection 2015. Review. — View Citation

Marotz CA, Zarrinpar A. Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation. Yale J Biol Med. 2016 Sep 30;89(3):383-388. eCollection 2016 Sep. Review. — View Citation

Nallu A, Sharma S, Ramezani A, Muralidharan J, Raj D. Gut microbiome in chronic kidney disease: challenges and opportunities. Transl Res. 2017 Jan;179:24-37. doi: 10.1016/j.trsl.2016.04.007. Epub 2016 Apr 30. Review. — View Citation

Ramezani A, Massy ZA, Meijers B, Evenepoel P, Vanholder R, Raj DS. Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target. Am J Kidney Dis. 2016 Mar;67(3):483-98. doi: 10.1053/j.ajkd.2015.09.027. Epub 2015 Nov 15. Review. — View Citation

Ranganathan N, Friedman EA, Tam P, Rao V, Ranganathan P, Dheer R. Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: a 6-month pilot scale trial in Canada. Curr Med Res Opin. 2009 Aug;25(8):1919-30. doi: 10.1185/03007990903069249. — View Citation

Rossi M, Johnson DW, Morrison M, Pascoe E, Coombes JS, Forbes JM, McWhinney BC, Ungerer JP, Dimeski G, Campbell KL. SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial. BMC Nephrol. 2014 Jul 4;15:106. doi: 10.1186/1471-2369-15-106. — View Citation

Sabatino A, Regolisti G, Brusasco I, Cabassi A, Morabito S, Fiaccadori E. Alterations of intestinal barrier and microbiota in chronic kidney disease. Nephrol Dial Transplant. 2015 Jun;30(6):924-33. doi: 10.1093/ndt/gfu287. Epub 2014 Sep 4. Review. — View Citation

Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, Ni Z, Nguyen TH, Andersen GL. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013 Feb;83(2):308-15. doi: 10.1038/ki.2012.345. Epub 2012 Sep 19. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Creatinine Clearance	Arrest CKD progression	6 months
Secondary	24-hour Urine Protein	Arrest CKD progression	6 months
Secondary	Serum Creatinine	Arrest CKD progression	6 months
Secondary	Hemoglobin	Arrest CKD progression	6 months
Secondary	Hematocrit	Arrest CKD progression	6 months
Secondary	Leukocytes	Arrest CKD progression	6 months
Secondary	Neutrophils	Arrest CKD progression	6 months
Secondary	Platelets	Arrest CKD progression	6 months
Secondary	Glucose	Arrest CKD progression	6 months
Secondary	Urea Nitrogen	Arrest CKD progression	6 months
Secondary	Uric Acid	Arrest CKD progression	6 months
Secondary	Albumin	Arrest CKD progression	6 months
Secondary	Reactive Protein C	Arrest CKD progression	6 months
Secondary	Chlorine	Arrest CKD progression	6 months
Secondary	Sodium	Arrest CKD progression	6 months
Secondary	Potassium	Arrest CKD progression	6 months
Secondary	Phosphorous	Arrest CKD progression	6 months
Secondary	pH Venous Gasometry	Arrest CKD progression	6 months
Secondary	CO2 pressure venous	Arrest CKD progression	6 months
Secondary	Venous Bicarbonate	Arrest CKD progression	6 months
Secondary	Base Excess	Arrest CKD progression	6 months
Secondary	Lactate	Arrest CKD progression	6 months