Effectiveness of Probiotics to Treat End Stage Renal Disease

Kidney Failure, Chronic Clinical Trial

Official title:

Effect of Probiotics on Modulating the Bacterial Translocation and Improving Micro-inflammation in Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02929225
• Other study ID #: XJTU1AF-CRS-2016-015
• Status: Completed
• Phase: Early Phase 1
• Start date: December 2016
• Est. completion date: March 30, 2018

Study information

• Verified date: August 2018
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intestinal microbiota has recently emerged as an important player in the progression and complications of chronic kidney disease(CKD). And drug therapy which selects the gut as a target has raised lots of concern. It has been reported that the composition of intestinal flora has changed in uremic patients. Specifically, imbalanced ecosystem has higher number of pathogens such as Clostridia, Enterobacteria,and lower number of beneficial microbes such as Lactobacilli and Bifidobacteria. This modification of intestinal flora can strongly increase transformation of amino acids into Uremic Retention solutes, e.g., indoxyl-sulfate (IS), p-cresyl sulfate (PCS), which are so called gut-derived uremic toxins. The dysbiosis also contributes to an increase in intestinal permeability by disrupting the colonic epithelial tight junction,which may subsequently lead to translocation of endotoxin and bacteria into the host's internal environment,resulting in systemic micro-inflammation.Also all of these can promote the progression of renal failure and the incidence of cardiovascular complications,renal osteodystrophy and anemia.Probiotics is defined by the World Health Organization as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host'. Probiotics are being increasingly used for various pathologic conditions.It is said that probiotics have a therapeutic role in maintaining a metabolically balanced gastrointestinal tract (GIT).And in our previous study,the investigators found that in uremic rats,lactobacillus acidophilus can relieve bacterial translocation and decrease the level of inflammatory markers.So our study is mainly designed to investigate whether probiotics can modulate the balance of intestinal ecosystem, prevent the bacterial translocation from gut and alleviate the systemic inflammation in hemodialysis(HD) patients.

Description:

This study is a single-centre, double-blind, placebo-controlled, randomised trial. Participants will undergo a 2 week run-in period, followed by randomisation to either probiotics supplements or placebo for 6 months. The study population are hemodialysis patients from Dialysis Department in First Affiliated Hospital of Xi'an Jiaotong University. The Dialysis Department have 400 patients who regularly come to receive dialysis therapy three times a week.It's relatively easy for us to follow up and collect data.Patients who meet the criteria and are able to provide informed consent will be recruited.Then computer-generated randomisation of participants to treatment order will be undertaken by an external statistical consultant. This process of allocation will conceal the randomisation order to researchers and participants. In addition, the supplements will be packed off-site with a generic label.

After randomization,baseline data will be collected and all participants will undergo face-to-face dietary education with a dietitian, incorporating standard hemodialysis education during the first week of run-in.In the week following, and throughout the intervention, patients will be encouraged to maintain stable protein and fibre intakes, with specific attention to maintaining the same sources of these nutrients.Participants' dietary intakes during the study will be assessed every month using a semi-quantitative food frequency questionnaire. And when the trial starts, questionnaires and biological samples will be performed and collected at the corresponding time. All serious adverse events will be reported to the ethics committee, whether deemed to be intervention related or not. Adherence to supplements will be measured by pill count every two weeks.

This study is an explorative clinical trial.And in the absence of any data about the effect of probiotics on hemodialysis patients intestinal and serum microbiota,sample size can't be calculated.Data will be reported as s mean±SD if normally distributed and as median(25-75% percentiles) if not. The Shapiro-Wilk test is performed to assess whether data are normally distributed. Statistical comparisons of normally distributed data are performed using Student's t-test. Mann-Whitney U-test is used to compare the rank variables measuring gastrointestinal symptoms in probiotics and placebo groups. The threshold for statistical significance is at p values <0.05. And an external statistical consultant from our Clinical Research Center will be involved in the data validation and analysis activities.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 30, 2018
• Est. primary completion date: January 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• maintenance hemodialysis patients(MHP),dialysis age>3 months;

• signed informed consent.

Exclusion Criteria:

• intolerance to whole milk and dairy products;

• patients with kidney transplant, with severe infections, sever heart disease and liver disease, malignancy, autoimmune disorders, severe malnutrition, or clinical conditions requiring artificial feeding;

• pregnant or nursing women;

• patients with known gastro-intestinal disease (i.e.,inflammatory bowel disease,crohn's disease,ulcerative colitis),receiving or have received radiation to the bowel or large bowel resection;

• use of antibiotics, prebiotics or probiotics in the past 4 weeks;

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Bifid Triple Viable Capsules
BIFICO is prescribed as a dose of 4 capsules twice daily in half hours after meals.

Other:
• placebo
placebo is also prescribed as a dose of 4 capsules twice daily

Locations

Country	Name	City	State
China	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University

Country where clinical trial is conducted

China, 

References & Publications (12)

Dou L, Cerini C, Brunet P, Guilianelli C, Moal V, Grau G, De Smet R, Vanholder R, Sampol J, Berland Y. P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines. Kidney Int. 2002 Dec;62(6):1999-2009. — View Citation

Ebel B, Lemetais G, Beney L, Cachon R, Sokol H, Langella P, Gervais P. Impact of probiotics on risk factors for cardiovascular diseases. A review. Crit Rev Food Sci Nutr. 2014;54(2):175-89. doi: 10.1080/10408398.2011.579361. Review. — View Citation

Food and Agriculture Organsization. Guidelines for the Evaluation of Probiotics in Food. Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food. Food and Agriculture Organization: London, 2002.

Hida M, Aiba Y, Sawamura S, Suzuki N, Satoh T, Koga Y. Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis. Nephron. 1996;74(2):349-55. — View Citation

Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 2015 Nov;88(5):958-66. doi: 10.1038/ki.2015.255. Epub 2015 Sep 16. Review. — View Citation

Niwa T, Ise M, Miyazaki T. Progression of glomerular sclerosis in experimental uremic rats by administration of indole, a precursor of indoxyl sulfate. Am J Nephrol. 1994;14(3):207-12. — View Citation

Shi K, Wang F, Jiang H, Liu H, Wei M, Wang Z, Xie L. Gut bacterial translocation may aggravate microinflammation in hemodialysis patients. Dig Dis Sci. 2014 Sep;59(9):2109-17. doi: 10.1007/s10620-014-3202-7. Epub 2014 May 15. — View Citation

Vanholder R, De Smet R, Glorieux G, Argilés A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jörres A, Lemke HD, Massy ZA, Passlick-Deetjen J, Rodriguez M, Stegmayr B, Stenvinkel P, Tetta C, Wanner C, Zidek W; European Uremic Toxin Work Group (EUTox). Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003 May;63(5):1934-43. 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

Vaziri ND, Yuan J, Rahimi A, Ni Z, Said H, Subramanian VS. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012 Jul;27(7):2686-93. doi: 10.1093/ndt/gfr624. Epub 2011 Nov 29. — View Citation

Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton). 2012 Nov;17(8):733-8. doi: 10.1111/j.1440-1797.2012.01647.x. — View Citation

Wei M, Wang Z, Liu H, Jiang H, Wang M, Liang S, Shi K, Feng J. Probiotic Bifidobacterium animalis subsp. lactis Bi-07 alleviates bacterial translocation and ameliorates microinflammation in experimental uraemia. Nephrology (Carlton). 2014 Aug;19(8):500-6. doi: 10.1111/nep.12272. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut microbiota	a faeces microbial analysis	Change from Baseline in faeces bacterial genomic DNA at 6 months
Secondary	plasma detection of bacterial genomic DNA,plasma and fecal metabolomics		Change from Baseline in faeces bacterial genomic DNA at 6 months, fecal and plasma metabolomics at baseline and 6 months
Secondary	plasma concentrations of inflammatory biomarkers(hs-C reactive protein,Interleukin(IL)-6,tumor necrosis factor(TNF)-a,endotoxin)		baseline,3 months and 6 months
Secondary	Gastrointestinal Symptom Rating Scale (GSRS),SF-36	Monitor Gastrointestinal symptoms and life quality	baseline,3 and 6 months