End Stage Renal Failure on DialysisNCT03770611
Effect of Prebiotics and/or Probiotics on Uremic Toxins and Inflammation Markers in Peritoneal Dialysis Patients
A study testing Probiotic, Prebiotic and Symbiotic in people with End Stage Renal Failure on Dialysis, run by Unidad de Investigacion Medica en Enfermedades Renales at 1 site in Mexico.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- End Stage Renal Failure on Dialysis
- What is being tested?
- Probiotic, Prebiotic and Symbiotic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteMexico
- Study dates
- 7 Jan 2019to Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >3 months on automated peritoneal dialysis treatment
- Signed informed consent
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Umae Hospital de Especialidades
Guadalajara, Jalisco, 44290
ALFONSO M CUETO-MANZANO, PhD, (52) 333668300 ext. 32204, a_cueto_manzano@hotmail.com
Fabiola Martín-del-Campo, MSc
About this study
Official title: Effect of a Nutritional Supplement of Probiotics and/or Prebiotics vs Placebo on Serum Concentrations of Uremic Toxins and Inflammatory Cytokines in Automated Peritoneal Dialysis Patients.
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.
Read more
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.
Read the detailed description
Objective:
The aim of the present study is to evaluate and to compare the effect of a nutritional supplement of probiotics and/or prebiotics on serum concentrations of uremic toxins and inflammatory markers compared to placebo, in automated peritoneal dialysis patients.
Sample size:
For the sample size calculation a mean differences formula was used, with a 95% confidence level, a 80% sample power and accuracy of 0.05. As a reference, the study of Salmean YA, 2015 was considered; in this study, the administration of pea fiber + inulin during 12 weeks in chronic kidney disease patients, significantly decreased (p<0.05) serum concentrations of p-cresol (5.82 ± 1.72 mg/L) in comparison to placebo (7.25 ± 1.74 mg/L). After substituting formula values and adding 20% of possible losses during follow-up, the sample size is: 28 patients.
Additionally, sample size calculation was made considering other outcomes. In the study of Xie LN, 2015, the administration of high-fermentable soluble fiber in ESRD patients on hemodialysis during 6 weeks, significantly decreased (p<0.05) inflammation markers: C-reactive protein (CRP), tumour necrosis factor alpha (TNFa) and interleukin 6 (IL-6) (4.8 ± 4.5 pg/mL, 10.1 ± 1.4 pg/mL, 31.8 ± 5.3 mg/L, respectively) compared to control group (9.5 ± 5.6 pg/mL, 13.1 ± 2.4 pg/mL, 51.5 ± 14.6 mg/L). After substituting the formula, sample size was 19, 7, and 5 for CRP, TNFa and IL-6, respectively.
Thus, the highest value was finally used: 28 patients for intervention group.
Statistical analysis:
Quantitative variables will be shown as mean and standard deviation or median (25-75 percentiles) according to their parametric or non-parametric distribution; Qualitative variables will be shown as frequency and percentage. Intergroup comparisons will be performed with χ2 or Fisher test for qualitative variables and one-way ANOVA or Kruskal-Wallis test for quantitative variables as appropriate. For intra-group comparisons Mc Nemar test will be used for qualitative variables and paired T-test, Wilcoxon, repeated-measures or Friedman ANOVA for quantitative variables as appropriate. An intention to treat analysis will be performed.
- Conditions
- End Stage Renal Failure on Dialysis
- Being tested
- Probiotic, Prebiotic, Symbiotic, Placebo
- Keywords
- dialysis, uremic toxin, inflammation, prebiotics, probiotics
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary 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
PrebioticDietary supplement
The prebiotic fiber is Agave inulin
SymbioticDietary supplement
The supplement is a combination of the probiotic product + the prebiotic fiber
PlaceboDietary supplement
The supplement is a combination of probiotic placebo and prebiotic fiber placebo. Placebo will consist on maltodextrin for both cases.
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Active comparator | Subjects receiving probiotic supplementation: 2x108 CFU probiotic bacteria + prebiotic placebo per day during 3 months Receives: Dietary Supplement: Probiotic |
| Prebiotic | Active comparator | Subjects receiving prebiotic supplementation: 20 g of prebiotic fiber + probiotic placebo per day during 3 months Receives: 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 Receives: Dietary Supplement: Symbiotic |
| Placebo | Placebo comparator | Subjects receiving placebo of probiotic and prebiotic per day during 3 months Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, 1 month and 3 months
Secondary outcomes (4)
Change in gut microbiota composition from basal to 1 and 3 months
Determination of fecal bacterial composition by DNA extraction and pyrosequencing analysis.
Measured: Baseline, 1 month and 3 months
Change in gastrointestinal symptoms from basal to 1 and 3 months
Measurement of appetite and frequency and severity of gastrointestinal symptoms (nausea, vomiting, bloating, diarrhea, constipation) by means of a gastrointestinal symptoms questionnaire.
Measured: Baseline, 1 month and 3 months
Change of inflammatory cytokines from basal to 1 and 3 months
Measurement of serum concentrations of inflammatory cytokines Interleukin-6 (pg/mL), Interleukin-10 (pg/mL) and Tumor Necrosis Factor alpha (pg/mL) by means of ELISA.
Measured: Baseline, 1 month and 3 months
Change of inflammatory cytokines from basal to 1 and 3 months
Measurement of serum concentrations of C-Reactive Protein (mg/L) by means of nephelometry.
Measured: Baseline, 1 month and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start7 Jan 2019 (estimated)
- Primary completionDec 2019 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal Failure on DialysisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Parallel assignment, patients in automated peritoneal dialysis will be randomly assigned to one of the four intervention groups: probiotic, prebiotic, symbiotic and placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unidad de Investigacion Medica en Enfermedades Renales
- Sponsor type
- University, hospital or other
- Collaborators
- Centro Universitario de Tonalá, Universidad de Colima
- Responsible party
- Principal investigator, Alfonso Martín Cueto Manzano, Unidad de Investigacion Medica en Enfermedades Renales
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03770611
- Sponsor's protocol ID
- UIMER003
- Status last verified
- Dec 2018
- First submitted
- 31 May 2018
- Last updated
- 10 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 22626821Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel). 2017 Jan 29;9(2):52. doi: 10.3390/toxins9020052.
PubMed 28146081Ito 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.
PubMed 24561478Vaziri 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.
PubMed 23258127Schepers 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.
PubMed 20093818Hauser 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.
PubMed 21160227Lin 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.
PubMed 26173073Soleimani 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.
PubMed 27927601Wang 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.
PubMed 25609654Salmean 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.
PubMed 25446837Xie 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.
PubMed 25785138Poesen 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.
PubMed 27100399Viramontes-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.
PubMed 25455039Cruz-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.
PubMed 25066654Rossi 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.
PubMed 26772193
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Nutritional Supplement of Probiotics and/or Prebiotics vs Placebo on Serum Concentrations of Uremic Toxins and Inflammatory Cytokines in Automated Peritoneal Dialysis Patients.
- ClinicalTrials.gov ID
- NCT03770611
- Acronym / sponsor ID
- UIMER003
- Conditions
- End Stage Renal Failure on Dialysis
- Keywords
- dialysis, uremic toxin, inflammation, prebiotics, probiotics
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Unidad de Investigacion Medica en Enfermedades RenalesUniversity, hospital or other
- Collaborators
- Centro Universitario de Tonalá, Universidad de Colima
- Study start
- 7 Jan 2019 (estimated)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 10 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objective:
The aim of the present study is to evaluate and to compare the effect of a nutritional supplement of probiotics and/or prebiotics on serum concentrations of uremic toxins and inflammatory markers compared to placebo, in automated peritoneal dialysis patients.
Sample size:
For the sample size calculation a mean differences formula was used, with a 95% confidence level, a 80% sample power and accuracy of 0.05. As a reference, the study of Salmean YA, 2015 was considered; in this study, the administration of pea fiber + inulin during 12 weeks in chronic kidney disease patients, significantly decreased (p<0.05) serum concentrations of p-cresol (5.82 ± 1.72 mg/L) in comparison to placebo (7.25 ± 1.74 mg/L). After substituting formula values and adding 20% of possible losses during follow-up, the sample size is: 28 patients.
Additionally, sample size calculation was made considering other outcomes. In the study of Xie LN, 2015, the administration of high-fermentable soluble fiber in ESRD patients on hemodialysis during 6 weeks, significantly decreased (p<0.05) inflammation markers: C-reactive protein (CRP), tumour necrosis factor alpha (TNFa) and interleukin 6 (IL-6) (4.8 ± 4.5 pg/mL, 10.1 ± 1.4 pg/mL, 31.8 ± 5.3 mg/L, respectively) compared to control group (9.5 ± 5.6 pg/mL, 13.1 ± 2.4 pg/mL, 51.5 ± 14.6 mg/L). After substituting the formula, sample size was 19, 7, and 5 for CRP, TNFa and IL-6, respectively.
Thus, the highest value was finally used: 28 patients for intervention group.
Statistical analysis:
Quantitative variables will be shown as mean and standard deviation or median (25-75 percentiles) according to their parametric or non-parametric distribution; Qualitative variables will be shown as frequency and percentage. Intergroup comparisons will be performed with χ2 or Fisher test for qualitative variables and one-way ANOVA or Kruskal-Wallis test for quantitative variables as appropriate. For intra-group comparisons Mc Nemar test will be used for qualitative variables and paired T-test, Wilcoxon, repeated-measures or Friedman ANOVA for quantitative variables as appropriate. An intention to treat analysis will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Parallel assignment, patients in automated peritoneal dialysis will be randomly assigned to one of the four intervention groups: probiotic, prebiotic, symbiotic and placebo
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Active comparator | Dietary Supplement: ProbioticSubjects receiving probiotic supplementation: 2x108 CFU probiotic bacteria + prebiotic placebo per day during 3 months |
| Prebiotic | Active comparator | Dietary Supplement: PrebioticSubjects receiving prebiotic supplementation: 20 g of prebiotic fiber + probiotic placebo per day during 3 months |
| Symbiotic | Experimental | Dietary Supplement: SymbioticSubjects receiving probiotic and prebiotic supplementation: 2x108 CFU probiotic bacteria + 20 g of prebiotic fiber per day during 3 months |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboSubjects receiving placebo of probiotic and prebiotic per day during 3 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- >3 months on automated peritoneal dialysis treatment
- Signed informed consent
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbioticThe 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 | Dietary supplement | Probiotic |
| PrebioticThe prebiotic fiber is Agave inulin | Dietary supplement | Prebiotic |
| SymbioticThe supplement is a combination of the probiotic product + the prebiotic fiber | Dietary supplement | Symbiotic |
| PlaceboThe supplement is a combination of probiotic placebo and prebiotic fiber placebo. Placebo will consist on maltodextrin for both cases. | Dietary supplement | Placebo |
Primary outcome
Change of uremic toxins from basal to 1 and 3 months
Time frame: Baseline, 1 month 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.
Change of uremic toxins from basal to 1 and 3 months
Time frame: Baseline, 1 month and 3 months
Measurement of serum concentrations of endotoxin (EU/mL) by means of Limulus amebocyte lisate test.
4 secondary outcomes
Change in gut microbiota composition from basal to 1 and 3 months
Time frame: Baseline, 1 month and 3 months
Change in gastrointestinal symptoms from basal to 1 and 3 months
Time frame: Baseline, 1 month and 3 months
Change of inflammatory cytokines from basal to 1 and 3 months
Time frame: Baseline, 1 month and 3 months
Change of inflammatory cytokines from basal to 1 and 3 months
Time frame: Baseline, 1 month and 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2018.
- Background: PubMed 22626821Duranton 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.
- Background: PubMed 28146081Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel). 2017 Jan 29;9(2):52. doi: 10.3390/toxins9020052.
- Background: PubMed 24561478Ito 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.
- Background: PubMed 23258127Vaziri 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.
- Background: PubMed 20093818Schepers 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.
- Background: PubMed 21160227Hauser 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.
- Background: PubMed 26173073Lin 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.
- Background: PubMed 27927601Soleimani 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.
- Background: PubMed 25609654Wang 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.
- Background: PubMed 25446837Salmean 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.
- Background: PubMed 25785138Xie 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.
- Background: PubMed 27100399Poesen 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.
- Individual participant dataSharing planned: Undecided
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RecruitingPhase 4
Empagliflozin in Heart Failure With Reduced Ejection Fraction and End Stage Renal Disease
Heart Failure With Reduced Ejection Fraction, End Stage Renal Disease on Dialysis
RecruitingPhase 2
Empagliflozin on Residual Kidney Function in Incident Peritoneal Dialysis Patients
End Stage Renal Disease on Dialysis, Peritoneal Dialysis Complication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic, Prebiotic and Symbiotic in people with End Stage Renal Failure on Dialysis, run by Unidad de Investigacion Medica en Enfermedades Renales at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alfonso M Cueto-Manzano, PhD (52 (33) 38097269, a_cueto_manzano@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of uremic toxins from basal to 1 and 3 months (time frame: Baseline, 1 month and 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03770611, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2018.