Effectiveness of Probiotics to Treat End Stage Renal Disease

NCT02929225 | Completed Early Phase 1

• 1 other identifier: XJTU1AF-CRS-2016-015
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Failure, Chronic

Keywords

bacterial translocation;micro-inflammation;hemodialysis

Outcome Measures

Primary Outcomes (1)

• Gut microbiota

  a faeces microbial analysis

  Change from Baseline in faeces bacterial genomic DNA at 6 months

Secondary Outcomes (3)

• 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

• plasma concentrations of inflammatory biomarkers(hs-C reactive protein,Interleukin(IL)-6,tumor necrosis factor(TNF)-α,endotoxin)

  baseline,3 months and 6 months

• Gastrointestinal Symptom Rating Scale (GSRS),SF-36

  baseline，3 and 6 months

Study Arms (2)

Bifid Triple Viable Capsules

EXPERIMENTAL

BIFICO(Shanghai Sine Pharmaceutical Laboratories Co.Ltd,S10950032), A biological preparation composed of triple viable microbe(Live combined Bifidobacterium, Lactobacillus and enterococcus capsules)

Drug: Bifid Triple Viable Capsules

placebo

PLACEBO COMPARATOR

placebo is also manufactured by Sine Pharmaceutical Laboratories,but only contains starch.And placebo is the same as probiotics in appearance,odor,flavor and color.

Other: placebo

Interventions

Bifid Triple Viable Capsules DRUG

BIFICO is prescribed as a dose of 4 capsules twice daily in half hours after meals.

Also known as: BIFICO,S10950032

Bifid Triple Viable Capsules

placebo OTHER

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

Also known as: placebo(Shanghai Sine Pharmaceutical Laboratories Co.Ltd)

placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• maintenance hemodialysis patients(MHP),dialysis age\>3 months;
• signed informed consent.

You may not qualify if:

• 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;

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, 710061, China

Location

Related Publications (12)

• 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. doi: 10.1159/000189334.

  PMID: 8893154 BACKGROUND

• 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.

  PMID: 22992469 BACKGROUND

• 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.

  PMID: 26376131 BACKGROUND

• 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.

  PMID: 22131233 BACKGROUND

• 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.

  PMID: 24828917 BACKGROUND

• 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.

  PMID: 22817644 BACKGROUND

• Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jorres 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. doi: 10.1046/j.1523-1755.2003.00924.x.

  PMID: 12675874 BACKGROUND

• 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. doi: 10.1046/j.1523-1755.2002.t01-1-00651.x.

  PMID: 12427124 BACKGROUND

• 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. doi: 10.1159/000168716.

  PMID: 7977482 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 24188267 BACKGROUND

• 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.

  PMID: 24787732 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hongli Jiang, professor

  First Affiliated Hospital Xi'an Jiaotong University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 11, 2016
• Study Start: December 1, 2016
• Primary Completion: January 30, 2018
• Study Completion: March 30, 2018
• Last Updated: August 8, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)