Effect of Prebiotics and/or Probiotics on Uremic Toxins and Inflammation Markers in Peritoneal Dialysis Patients

NCT03770611 | Unknown

• 1 other identifier: UIMER003
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

End-stage renal disease (ESRD) is a world public health problem, with high morbidity and mortality. Cardiovascular disease is the main cause of mortality in ESRD; uremic toxin retention and inflammation are considered non-traditional risk factors, as they have an active role in atherosclerosis and vascular calcification pathogenesis in dialysis patients. Uremic toxins may be generated by internal protein metabolism, however, some toxins that can't be efficiently eliminated by dialysis such as indoxyl sulphate and p-cresyl sulphate (protein bound toxins), are generated by the microbial metabolism in the large intestine by proteolytic bacteria, and may diffuse easily through the intestinal lumen, as a leaky gut characterizes kidney disease. The gut has been recognized as a potential source of inflammation in ESRD patients; accumulation of nitrogen compounds, presence of gastrointestinal symptoms, dietary changes and multiple drugs and supplements use, stimulates microbiota alterations as bacterial overgrowth and translocation. These phenomena, may active the immune system, promoting local and systemic inflammation, which in turn has negative effects increasing endothelial dysfunction, muscle catabolism, insulin and erythropoietin resistance, and decreases appetite. Some methods have been proposed to decrease inflammation and uremic toxin accumulation, as more efficient dialysis and anti-inflammatory drugs; however, some of them have limited efficacy and high cost. Nutritional treatments focused on modifying intestinal environment, as pre- and probiotics have promising effects by altering production and absorption of uremic toxins and decreasing inflammation; nevertheless, there is scarce information regarding its use and their role in ESRD, particularly in peritoneal dialysis, which is a widely used therapy in México. Furthermore, there is no clinical study comparing the effectiveness of prebiotics, probiotics, and symbiotics on serum concentrations of uremic toxins and inflammation in ESRD patients. It is possible that the administration of a nutritional supplement of probiotics and/or prebiotics decreases the serum concentrations of uremic toxins and inflammation markers in ESRD patients on automated peritoneal dialysis compared to placebo.

Conditions

End Stage Renal Failure on Dialysis

Keywords

dialysis; uremic toxin; inflammation; prebiotics; probiotics

Outcome Measures

Primary Outcomes (2)

• Change of uremic toxins from basal to 1 and 3 months

  Measurement of serum concentrations of the uremic toxins p-cresyl sulphate (mg/dL) and indoxyl sulphate (mg/dL) by means of liquid chromatography.

  Baseline, 1 month and 3 months

• Change of uremic toxins from basal to 1 and 3 months

  Measurement of serum concentrations of endotoxin (EU/mL) by means of Limulus amebocyte lisate test.

  Baseline, 1 month and 3 months

Secondary Outcomes (4)

• Change in gut microbiota composition from basal to 1 and 3 months

  Baseline, 1 month and 3 months

• Change in gastrointestinal symptoms from basal to 1 and 3 months

  Baseline, 1 month and 3 months

• Change of inflammatory cytokines from basal to 1 and 3 months

  Baseline, 1 month and 3 months

• Change of inflammatory cytokines from basal to 1 and 3 months

  Baseline, 1 month and 3 months

Study Arms (4)

Probiotic

ACTIVE COMPARATOR

Subjects receiving probiotic supplementation: 2x108 CFU probiotic bacteria + prebiotic placebo per day during 3 months

Dietary Supplement: Probiotic

Prebiotic

ACTIVE COMPARATOR

Subjects receiving prebiotic supplementation: 20 g of prebiotic fiber + probiotic placebo per day during 3 months

Dietary Supplement: Prebiotic

Symbiotic

EXPERIMENTAL

Subjects receiving probiotic and prebiotic supplementation: 2x108 CFU probiotic bacteria + 20 g of prebiotic fiber per day during 3 months

Dietary Supplement: Symbiotic

Placebo

PLACEBO COMPARATOR

Subjects receiving placebo of probiotic and prebiotic per day during 3 months

Dietary Supplement: Placebo

Interventions

Probiotic DIETARY_SUPPLEMENT

The probiotic supplement is composed of the following bacterial strains: Bacillus coagulans, Bacillus subtilis, Bifidobacterium (B) bifidum, B. breve, B. longum, Lactobacillus (L) acidophilus, L. brevis, L. casei, L. helveticus, L. Paracasei, L plantarum, L. rhamnosus, L. salivarus, Lactococcus lactis, Pediococcus acidilactici, Pediococcus parvulus, Weisella confusa, Weisella paramesenteroides

Probiotic

Prebiotic DIETARY_SUPPLEMENT

The prebiotic fiber is Agave inulin

Prebiotic

Symbiotic DIETARY_SUPPLEMENT

The supplement is a combination of the probiotic product + the prebiotic fiber

Symbiotic

Placebo DIETARY_SUPPLEMENT

The supplement is a combination of probiotic placebo and prebiotic fiber placebo. Placebo will consist on maltodextrin for both cases.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>3 months on automated peritoneal dialysis treatment
• Signed informed consent

You may not qualify if:

• ESRD of inflammatory cause (lupus, vasculitis, collagenopathies)
• Intake of probiotics, prebiotics or fiber in the last 3 months
• Use of anti-inflammatory drugs or nutritional supplements (immunossuppresants, pentoxifylline, NSAIDs, omega-3)
• Treated with antibiotics or sevelamer
• Treated with research drugs or participants in any clinical trial
• Peritonitis or active infection 2 weeks prior the study
• Any medical condition affecting intestinal absorption (inflammatory bowel disease, short bowel syndrome, bariatric surgery) or severe dysmotility
• Severe malnutrition
• Previous kidney transplantation
• Serious diseases altering the fina outcomes of the study: decompensated heart failure, chronic liver disease, cancer, AIDS.

Sponsors & Collaborators

• Unidad de Investigacion Medica en Enfermedades Renales: lead
• Centro Universitario de Tonalá: collaborator
• Universidad de Colima: collaborator

Study Sites (1)

Umae Hospital de Especialidades

Guadalajara, Jalisco, 44290, Mexico

Location

Related Publications (16)

• Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A; European Uremic Toxin Work Group. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24.

  PMID: 22626821 BACKGROUND

• Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel). 2017 Jan 29;9(2):52. doi: 10.3390/toxins9020052.

  PMID: 28146081 BACKGROUND

• Ito S, Yoshida M. Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients. Toxins (Basel). 2014 Feb 20;6(2):665-78. doi: 10.3390/toxins6020665.

  PMID: 24561478 BACKGROUND

• Vaziri ND, Yuan J, Norris K. Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. Am J Nephrol. 2013;37(1):1-6. doi: 10.1159/000345969. Epub 2012 Dec 19.

  PMID: 23258127 BACKGROUND

• Schepers E, Glorieux G, Vanholder R. The gut: the forgotten organ in uremia? Blood Purif. 2010;29(2):130-6. doi: 10.1159/000245639. Epub 2010 Jan 8.

  PMID: 20093818 BACKGROUND

• Hauser AB, Stinghen AE, Goncalves SM, Bucharles S, Pecoits-Filho R. A gut feeling on endotoxemia: causes and consequences in chronic kidney disease. Nephron Clin Pract. 2011;118(2):c165-72; discussion c172. doi: 10.1159/000321438. Epub 2010 Dec 16.

  PMID: 21160227 BACKGROUND

• 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.

  PMID: 26173073 BACKGROUND

• Soleimani A, Zarrati Mojarrad M, Bahmani F, Taghizadeh M, Ramezani M, Tajabadi-Ebrahimi M, Jafari P, Esmaillzadeh A, Asemi Z. Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects. Kidney Int. 2017 Feb;91(2):435-442. doi: 10.1016/j.kint.2016.09.040. Epub 2016 Dec 4.

  PMID: 27927601 BACKGROUND

• Wang IK, Wu YY, Yang YF, Ting IW, Lin CC, Yen TH, Chen JH, Wang CH, Huang CC, Lin HC. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial. Benef Microbes. 2015;6(4):423-30. doi: 10.3920/BM2014.0088. Epub 2015 Feb 12.

  PMID: 25609654 BACKGROUND

• Salmean YA, Segal MS, Palii SP, Dahl WJ. Fiber supplementation lowers plasma p-cresol in chronic kidney disease patients. J Ren Nutr. 2015 May;25(3):316-20. doi: 10.1053/j.jrn.2014.09.002. Epub 2014 Nov 5.

  PMID: 25446837 BACKGROUND

• Xie LM, Ge YY, Huang X, Zhang YQ, Li JX. Effects of fermentable dietary fiber supplementation on oxidative and inflammatory status in hemodialysis patients. Int J Clin Exp Med. 2015 Jan 15;8(1):1363-9. eCollection 2015.

  PMID: 25785138 BACKGROUND

• Poesen R, Evenepoel P, de Loor H, Delcour JA, Courtin CM, Kuypers D, Augustijns P, Verbeke K, Meijers B. The Influence of Prebiotic Arabinoxylan Oligosaccharides on Microbiota Derived Uremic Retention Solutes in Patients with Chronic Kidney Disease: A Randomized Controlled Trial. PLoS One. 2016 Apr 21;11(4):e0153893. doi: 10.1371/journal.pone.0153893. eCollection 2016.

  PMID: 27100399 BACKGROUND

• Viramontes-Horner D, Marquez-Sandoval F, Martin-del-Campo F, Vizmanos-Lamotte B, Sandoval-Rodriguez A, Armendariz-Borunda J, Garcia-Bejarano H, Renoirte-Lopez K, Garcia-Garcia G. Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on presence and severity of gastrointestinal symptoms in hemodialysis patients. J Ren Nutr. 2015 May;25(3):284-91. doi: 10.1053/j.jrn.2014.09.008. Epub 2014 Nov 6.

  PMID: 25455039 BACKGROUND

• Cruz-Mora J, Martinez-Hernandez NE, Martin del Campo-Lopez F, Viramontes-Horner D, Vizmanos-Lamotte B, Munoz-Valle JF, Garcia-Garcia G, Parra-Rojas I, Castro-Alarcon 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.

  PMID: 25066654 BACKGROUND

• Rossi M, Johnson DW, Morrison M, Pascoe EM, Coombes JS, Forbes JM, Szeto CC, McWhinney BC, Ungerer JP, Campbell KL. Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. Clin J Am Soc Nephrol. 2016 Feb 5;11(2):223-31. doi: 10.2215/CJN.05240515. Epub 2016 Jan 15.

  PMID: 26772193 BACKGROUND

• Cooper TE, Khalid R, Chan S, Craig JC, Hawley CM, Howell M, Johnson DW, Jaure A, Teixeira-Pinto A, Wong G. Synbiotics, prebiotics and probiotics for people with chronic kidney disease. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD013631. doi: 10.1002/14651858.CD013631.pub2.

  PMID: 37870148 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

Probiotics; Prebiotics

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides

Central Study Contacts

Alfonso M Cueto-Manzano, PhD

CONTACT

52 (33) 38097269; a_cueto_manzano@hotmail.com

Fabiola Martín-del-Campo, MSc

CONTACT

52 (33) 10711190; fabi_mc@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patient Blinding: Patients in automated peritoneal dialysis will be blinded to the intervention they will receive. Evaluator Blinding: The principal investigator and the Doctorate program student will be blinded to the intervention that patients will receive (probiotic, prebiotic, symbiotic or placebo). Care providers will be blinded to the intervention groups.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Biomedical Research Unit 02

Model Details: Parallel assignment, patients in automated peritoneal dialysis will be randomly assigned to one of the four intervention groups: probiotic, prebiotic, symbiotic and placebo

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: December 10, 2018
• Study Start: January 7, 2019
• Primary Completion: December 1, 2019
• Study Completion: August 1, 2020
• Last Updated: December 10, 2018

Record last verified: 2018-12

Locations

ME (1)