Prebiotic in Chronic Kidney Disease Patients

NCT ID: NCT02364869

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2016-12-31

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.

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.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Fructooligosaccharide

12g daily, for 12 weeks

Group Type: EXPERIMENTAL

Fructooligosaccharide

Intervention Type: DIETARY_SUPPLEMENT

Patients will be evaluated at baseline, week 6 and 12.

Maltodextrin

12g daily, for 12 weeks

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: DIETARY_SUPPLEMENT

Placebo Comparator. Patients will be evaluated at baseline, week 6 and 12.

Interventions

Fructooligosaccharide

Patients will be evaluated at baseline, week 6 and 12.

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin

Placebo Comparator. Patients will be evaluated at baseline, week 6 and 12.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Prebiotic

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidade Federal do Paraná

OTHER

Sponsor Role: collaborator

Pontifícia Universidade Católica do Paraná

OTHER

Sponsor Role: collaborator

Federal University of São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Lilian Cuppari

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lilian Cupari, PhD

Role: PRINCIPAL_INVESTIGATOR

Affiliate professor of Federal University of São Paulo

Locations

Federal University of São Paulo

São Paulo, São Paulo, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 37870148 (View on PubMed)

Other Identifiers

MCTI/CNPQ: 449614/2014-0

Identifier Type: -

Identifier Source: org_study_id