Inulin and Protein Fermentation in Hemodialysis Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Dietary Supplement: BENEO synergy1


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I<br>BENEO synergy1 | Dietary Supplement: BENEO synergy1<br>* 50/50 v/v inulin/oligofructose 10 gram BID<br>* Other names: Synergy1;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food supplement, Haemodialysis