Clinical trial NCT02141815: AXOS and Microbial Metabolites in CKD
Official title: The Effect of Arabinoxylan-oligosaccharides (AXOS) on Intestinal Generation of Microbial Metabolites in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2014-05-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Chronic kidney disease is associated with the accumulation of various metabolites, i.e., uremic retention solutes. Evidence is mounting that the colonic microbiota contributes substantially to these uremic retention solutes. Indoxyl sulfate and p-cresyl sulfate are among the most extensively studied gut microbial metabolites, and are associated with cardiovascular disease, overall mortality and chronic kidney disease progression. The most important regulator of colonic bacterial metabolism is nutrient availability and especially the ratio of available fermentable carbohydrate to nitrogen, which can be modified by intake of so-called prebiotics (non-digestible food ingredients). Arabinoxylan oligosaccharides (AXOS) are a recently developed group of prebiotics, and already demonstrated a decreasing effect on intestinal generation of p-cresol in healthy individuals. Whether prebiotics in general, and AXOS more specifically, can influence intestinal generation of microbial metabolites in predialysis patients has not been studied to date. An interventional study with AXOS will therefore be initiated to test the hypothesis that AXOS can decrease intestinal generation and serum concentrations of microbial metabolites in patients with CKD not yet on dialysis.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 and ≤ 85 years
* Chronic kidney disease stage 3b-4, i.e., with estimated glomerular filtration rate (CKD-epi) between 45 - 15 ml/min/m² 29
* Written informed consent

Exclusion Criteria:

* History of organic gastro-intestinal disease (e.g., inflammatory bowel disease, malignancy)
* History of colonic surgery
* Recipient of a renal or other solid organ transplant
* Use of pre-/pro-/syn- or antibiotics in preceding 4 weeks

Primary outcomes:
measure: Serum levels of p-cresol and indole derivatives
timeFrame: After 4 weeks of intervention
Secondary outcomes:
measure: Urinary excretion rates of p-cresol and indole derivatives
timeFrame: After 4 weeks of intervention
measure: Insuline resistance
timeFrame: After 4 weeks of intervention
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Ruben Poesen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Björn Meijers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Poesen R, Evenepoel P, de Loor H, Delcour JA, Courtin CM, Kuypers D, Augustijns P, Verbeke K, Meijers B. The Influence of Prebiotic Arabinoxylan Oligosaccharides on Microbiota Derived Uremic Retention Solutes in Patients with Chronic Kidney Disease: A Randomized Controlled Trial. PLoS One. 2016 Apr 21;11(4):e0153893. doi: 10.1371/journal.pone.0153893. eCollection 2016.