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Prebiotic in Chronic Kidney Disease Patients

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ClinicalTrials.gov Identifier: NCT02364869
Recruitment Status : Completed
First Posted : February 18, 2015
Last Update Posted : April 7, 2017
Sponsor:
Collaborators:
Universidade Federal do Paraná
Pontifícia Universidade Católica do Paraná
Information provided by (Responsible Party):
Lilian Cuppari, Federal University of São Paulo

Brief Summary:
This 12-week double-blind randomized controlled clinical trial aims to investigate the effect of a prebiotic (fructooligosaccharide - FOS) on serum and urinary levels of uremic toxins (p-cresyl sulfate and indoxyl sulfate) of non-dialysis dependent CKD patients, and the impact of such intervention on cardiovascular markers, intestinal permeability, endotoxemia and inflammatory response.

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Dietary Supplement: Fructooligosaccharide Dietary Supplement: Maltodextrin Not Applicable

Detailed Description:
Intestinal microbiome has been considered a new therapeutic target for chronic kidney disease (CKD) due to its potential role on the metabolic disturbances associated to the disease. The abnormalities in the microbiota, frequently found in patients with CKD, contribute to the accumulation of uremic toxins derived from the unbalanced fermentation of nitrogen compounds in relation to the non-digestible carbohydrates. Among them, p-cresyl sulfate and indoxyl sulfate have been associated with inflammation, kidney disease progression, endothelial dysfunction and increased risk of death in this population. Preliminary studies especially on hemodialysis have shown that the use of prebiotic, probiotic and symbiotic may represent a promising intervention due to their beneficial effect as modulators of the intestinal microbiota that might promote a reduction on serum concentration of p-cresyl sulfate and indoxyl sulfate. In comparison to probiotic, prebiotic have the advantage to stimulate the host's microbiota and to occur naturally in several foods. In the context of CKD, the use of prebiotics has been poorly investigated. Therefore, the primary aim of this study is to investigate the effect of a prebiotic (fructooligosaccharide - FOS) on serum and urinary levels of p-cresyl sulfate and indoxyl sulfate of non-dialysis dependent CKD patients. As a secondary aim we will investigate the impact of such intervention on cardiovascular markers, intestinal permeability, endotoxemia and inflammatory response. This is a 12-week double-blind randomized controlled clinical trial. Fifty non-diabetic patients with CKD stages 3a and 4 will be randomly assigned to a 12 g/day of FOS or maltodextrin (placebo). The serum and urinary concentrations of p-cresyl sulfate and indoxyl sulfate will be determined by high performance liquid chromatography (HPLC). The assessment of endothelial function includes ultrasonography of the brachial artery, measurement of plasma and urinary nitric oxide, monocyte chemoattractant protein 1 (MCP1), stromal cell-derived factor 1 alpha (SDF1α), oxide - trimethylamine N- (TMAO), ambulatory blood pressure monitoring (ABPM) and pulse wave velocity (PWV). The serum intestinal trophic markers (glucagon-like peptide 2 - GLP2 - and epidermal growth factor - EGF), intestinal permeability (Zonulin), endotoxemia and inflammation (IL-6 and CRP) will be determined by ELISA. Food intake will be assessed by 3-day food records. Protein intake will be estimated by calculating the protein equivalent of nitrogen appearance (PNA). The Bristol Scale, the Roma III Criteria and the Gastrointestinal Symptoms Rating Scale will be applied to evaluate gastrointestinal effects during the follow-up. The subjective global assessment questionnaire, the spectroscopic bioimpedance analysis and the handgrip strength will be applied to evaluate the nutritional status of the patients.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Effect of Prebiotic (Fructooligosaccharide) on Uremic Toxins and Cardiovascular Markers of Chronic Kidney Disease Patients
Study Start Date : May 2015
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Experimental: Fructooligosaccharide
12g daily, for 12 weeks
Dietary Supplement: Fructooligosaccharide
Patients will be evaluated at baseline, week 6 and 12.
Other Name: Prebiotic

Placebo Comparator: Maltodextrin
12g daily, for 12 weeks
Dietary Supplement: Maltodextrin
Placebo Comparator. Patients will be evaluated at baseline, week 6 and 12.




Primary Outcome Measures :
  1. Uremic toxicity evaluated by serum and urinary levels of p-cresyl sulfate and indoxyl sulfate [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Endotoxemia measured by serum levels of lipopolysaccharides [ Time Frame: 12 weeks ]
  2. Intestinal permeability evaluated by serum levels of Zonulin [ Time Frame: 12 weeks ]
  3. Intestinal epithelium evaluated by serum levels of glucagon-like peptide 2 (GLP2) [ Time Frame: 12 weeks ]
  4. Intestinal epithelium evaluated by serum levels of epidermal growth factor (EGF). [ Time Frame: 12 weeks ]
  5. Inflammation measured by serum levels of Interleukin-6 (IL-6) [ Time Frame: 12 weeks ]
  6. Inflammation measured by serum levels of c-reactive protein (CRP) [ Time Frame: 12 weeks ]
  7. Endothelial function evaluated by ultrasonography of the brachial artery [ Time Frame: 12 weeks ]
  8. Endothelial function evaluated by blood pressure monitoring (ABPM) [ Time Frame: 12 weeks ]
  9. Endothelial function evaluated by pulse wave velocity (PWV). [ Time Frame: 12 weeks ]
  10. Endothelial function evaluated by plasma and urinary levels of nitric oxide [ Time Frame: 12 weeks ]
  11. Endothelial function evaluated by plasma and urinary levels of monocyte chemoattractant protein 1 (MCP1) [ Time Frame: 12 weeks ]
  12. Endothelial function evaluated by plasma and urinary levels of stromal cell-derived factor 1 alpha (SDF1α) [ Time Frame: 12 weeks ]
  13. Endothelial function evaluated by plasma and urinary levels of oxide - trimethylamine N- (TMAO) [ Time Frame: 12 weeks ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 80 years
  • Estimated glomerular filtration rate between 45 to 15 ml/min/1,73m².

Exclusion Criteria:

  • diabetes mellitus, malignance, severe liver disease, autoimmune diseases, congestive heart failure class III / IV, HIV, history of gastrointestinal disease
  • use of phosphate binders, laxatives or prebiotic, probiotic, symbiotic, antibiotics, immunosuppressants and / or anti-inflammatory drugs three months preceding the study.
  • patients using laxatives who refuse to stop treatment during the follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02364869


Locations
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Brazil
Federal University of São Paulo
São Paulo, Brazil
Sponsors and Collaborators
Federal University of São Paulo
Universidade Federal do Paraná
Pontifícia Universidade Católica do Paraná
Investigators
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Principal Investigator: Lilian Cupari, PhD Affiliate professor of Federal University of São Paulo

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Responsible Party: Lilian Cuppari, PhD, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT02364869     History of Changes
Other Study ID Numbers: MCTI/CNPQ: 449614/2014-0
First Posted: February 18, 2015    Key Record Dates
Last Update Posted: April 7, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Lilian Cuppari, Federal University of São Paulo:
P-cresyl sulfate
Indoxyl sulfate
Intestine
Endothelial function
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency