Inulin and Protein Fermentation in Hemodialysis Patients

A Phase 1/2 Study on the Effects of BENEO synergy1 on the Generation Rate and Serum Concentration of P-cresol and Related Protein-fermentation Endproducts in Haemodialysis Patients

An important group of protein-bound uremic retention solutes originate from protein fermentation in the colon. P-cresol is a putrefaction metabolite of tyrosine. Indole is generated by fermentation of tryptophan. After absorption, the majority of p-cresol and indole are further metabolised and conjugated to form p-cresylsulphate and indoxyl sulphate. There is clear evidence, both in vitro and in vivo, that accumulation of these conjugated fermentation metabolites in kidney disease is correlated with clinical (cardiovascular) endpoints.

Bacterial protein fermentation can be influenced by altering the colonic microenvironment, influencing the ratio of available carbohydrates to nitrogen, by shortening the colonic transit time or a combination of these. From a theoretical point of view, functional foods, i.e. pro-, pre- and synbiotics, fulfil these criteria.

Prebiotics have been defined as non-digestible food ingredients that beneficially affect the host by selectively stimulating growth, and/or activity, of one or a restricted number of bacteria in the colon. Dietary fibre may suppress the generation of bacterial protein fermentation either by altering the colonic microenvironment or by shortening the colonic transit time. Animal and clinical studies evaluating the effect of dietary fibre supplements on the generation of bacterial fermentation metabolites have provided conflicting results. These discrepancies may be related to specific properties of the dietary fibre investigated. Dietary fibre may impair protein assimilation and the fermentability may vary to a substantial extent.

Inulin and oligofructose have attracted much attention recently as nonabsorbable carbohydrates with prebiotic properties. When inulin and oligofructose were added to a controlled diet, significant increases were noted in colonic bifidobacterial populations, and it has been proposed that these changes promote both colonic and systemic health through modification of the intestinal microflora. Inulin and oligofructose are rapidly and completely fermented by the colonic microflora with the production of acetate and other short-chain fatty acids. In healthy individuals, supplementation with a mixture of inulin and oligofructose was shown to lower p-cresol generation. Although data in healthy volunteers are promising, no data are available in hemodialysis patients.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: BENEO synergy1

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic hemodialysis patients on maintenance dialysis treatment.
• 18 years of age or older
• Written informed consent

Exclusion Criteria:

• Use of pre-/pro-/syn- or antibiotics in preceding 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I; BENEO synergy1	Dietary supplement: BENEO synergy1; 50/50 v/v inulin/oligofructose 10 gram BID; Other Names: Synergy1; BENEO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease p-cresol serum concentration	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Decreased generation rate of p-cresol	4 weeks
Decreased serum concentration of related uremic retention solutes	4 weeks
Change in bowel habits as measured by validated constipation scores	4 weeks
inflammation (c-reactive protein)	4 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Pieter Evenepoel, MD, PhD, Universitaire Ziekenhuizen KU Leuven; Principal Investigator: Bjorn Meijers, MD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Meijers BK, Bammens B, De Moor B, Verbeke K, Vanrenterghem Y, Evenepoel P. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int. 2008 May;73(10):1174-80. doi: 10.1038/ki.2008.31. Epub 2008 Feb 27.
• De Preter V, Vanhoutte T, Huys G, Swings J, De Vuyst L, Rutgeerts P, Verbeke K. Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G358-68. doi: 10.1152/ajpgi.00052.2006. Epub 2006 Sep 21.
• Meijers BK, De Preter V, Verbeke K, Vanrenterghem Y, Evenepoel P. p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrol Dial Transplant. 2010 Jan;25(1):219-24. doi: 10.1093/ndt/gfp414. Epub 2009 Aug 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: June 10, 2008
• First Submitted That Met QC Criteria: June 10, 2008
• First Posted (Estimate): June 12, 2008

Study Record Updates

• Last Update Posted (Estimate): September 15, 2011
• Last Update Submitted That Met QC Criteria: September 14, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Food supplement; Haemodialysis
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: ML3534