Prebiotic in Chronic Kidney Disease Patients

Chronic Kidney Disease Clinical Trial

Official title:

Effect of Prebiotic (Fructooligosaccharide) on Uremic Toxins and Cardiovascular Markers of Chronic Kidney Disease Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02364869
• Other study ID #: MCTI/CNPQ: 449614/2014-0
• Status: Completed
• Phase: N/A
• First received: January 13, 2015
• Last updated: April 6, 2017
• Start date: May 2015
• Est. completion date: December 2016

Study information

• Verified date: April 2017
• Source: Federal University of São Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Fructooligosaccharide
Patients will be evaluated at baseline, week 6 and 12.
• Maltodextrin
Placebo Comparator. Patients will be evaluated at baseline, week 6 and 12.

Locations

Country	Name	City	State
Brazil	Federal University of São Paulo	São Paulo

Sponsors (3)

Lead Sponsor	Collaborator
Federal University of São Paulo	Pontifícia Universidade Católica do Paraná, Universidade Federal do Paraná

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Uremic toxicity evaluated by serum and urinary levels of p-cresyl sulfate and indoxyl sulfate		12 weeks
Secondary	Endotoxemia measured by serum levels of lipopolysaccharides		12 weeks
Secondary	Intestinal permeability evaluated by serum levels of Zonulin		12 weeks
Secondary	Intestinal epithelium evaluated by serum levels of glucagon-like peptide 2 (GLP2)		12 weeks
Secondary	Intestinal epithelium evaluated by serum levels of epidermal growth factor (EGF).		12 weeks
Secondary	Inflammation measured by serum levels of Interleukin-6 (IL-6)		12 weeks
Secondary	Inflammation measured by serum levels of c-reactive protein (CRP)		12 weeks
Secondary	Endothelial function evaluated by ultrasonography of the brachial artery		12 weeks
Secondary	Endothelial function evaluated by blood pressure monitoring (ABPM)		12 weeks
Secondary	Endothelial function evaluated by pulse wave velocity (PWV).		12 weeks
Secondary	Endothelial function evaluated by plasma and urinary levels of nitric oxide		12 weeks
Secondary	Endothelial function evaluated by plasma and urinary levels of monocyte chemoattractant protein 1 (MCP1)		12 weeks
Secondary	Endothelial function evaluated by plasma and urinary levels of stromal cell-derived factor 1 alpha (SDF1a)		12 weeks
Secondary	Endothelial function evaluated by plasma and urinary levels of oxide - trimethylamine N- (TMAO)		12 weeks