Clinical trial NCT00695513: Inulin and Protein Fermentation in Hemodialysis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Kidney Disease
Keywords: Food supplement
Haemodialysis
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2008-06-12
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Decrease p-cresol serum concentration
timeFrame: 4 weeks
Secondary outcomes:
measure: Decreased generation rate of p-cresol
timeFrame: 4 weeks
measure: Decreased serum concentration of related uremic retention solutes
timeFrame: 4 weeks
measure: Change in bowel habits as measured by validated constipation scores
timeFrame: 4 weeks
measure: inflammation (c-reactive protein)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Pieter Evenepoel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Bjorn Meijers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.